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Sample records for dynamics regulate multiple

  1. Multiple mechanisms regulate NuMA dynamics at spindle poles.

    Science.gov (United States)

    Kisurina-Evgenieva, Olga; Mack, Gary; Du, Quansheng; Macara, Ian; Khodjakov, Alexey; Compton, Duane A

    2004-12-15

    The large coiled-coil protein NuMA plays an essential role in organizing microtubule minus ends at spindle poles in vertebrate cells. Here, we use both in vivo and in vitro methods to examine NuMA dynamics at mitotic spindle poles. Using fluorescence recovery after photobleaching, we show that an exogenously expressed green-fluorescent-protein/NuMA fusion undergoes continuous exchange between soluble and spindle-associated pools in living cells. These dynamics require cellular energy and display an average half-time for fluorescence recovery of approximately 3 minutes. To explore how NuMA dynamics at spindle poles is regulated, we exploited the association of NuMA with microtubule asters formed in mammalian mitotic extracts. Using a monoclonal antibody specific for human NuMA, we followed the fate of human NuMA associated with microtubule asters upon dilution with a hamster mitotic extract. Consistent with in vivo data, this assay shows that NuMA can be displaced from the core of pre-assembled asters into the soluble pool. The half-time of NuMA displacement from asters under these conditions is approximately 5 minutes. Using this assay, we show that protein kinase activity and the NuMA-binding protein LGN regulate the dynamic exchange of NuMA on microtubule asters. Thus, the dynamic properties of NuMA are regulated by multiple mechanisms including protein phosphorylation and binding to the LGN protein, and the rate of exchange between soluble and microtubule-associated pools suggests that NuMA associates with an insoluble matrix at spindle poles.

  2. Safe Dynamic Multiple Inheritance

    DEFF Research Database (Denmark)

    Ernst, Erik

    2002-01-01

    Multiple inheritance and similar mechanisms are usually only supported at compile time in statically typed languages. Nevertheless, dynamic multiple inheritance would be very useful in the development of complex systems, because it allows the creation of many related classes without an explosion ...... of operands the '&' operator fails; as a result, dynamic creation of new classes and methods was considered a dangerous operation in all cases. This paper presents a large and useful category of combinations, and proves that combinations in this category will always succeed....

  3. Multiple time scale dynamics

    CERN Document Server

    Kuehn, Christian

    2015-01-01

    This book provides an introduction to dynamical systems with multiple time scales. The approach it takes is to provide an overview of key areas, particularly topics that are less available in the introductory form.  The broad range of topics included makes it accessible for students and researchers new to the field to gain a quick and thorough overview. The first of its kind, this book merges a wide variety of different mathematical techniques into a more unified framework. The book is highly illustrated with many examples and exercises and an extensive bibliography. The target audience of this  book are senior undergraduates, graduate students as well as researchers interested in using the multiple time scale dynamics theory in nonlinear science, either from a theoretical or a mathematical modeling perspective. 

  4. Regulating multiple externalities

    DEFF Research Database (Denmark)

    Waldo, Staffan; Jensen, Frank; Nielsen, Max

    2016-01-01

    Open access is a well-known externality problem in fisheries causing excess capacity and overfishing. Due to global warming, externality problems from CO2 emissions have gained increased interest. With two externality problems, a first-best optimum can be achieved by using two regulatory...... instruments. However, solving the open-access externality problem also affects CO2 emissions. By using a bio-economic model covering Iceland, Norway, Denmark, Sweden, and the Faroe Islands, it is shown that regulations of the open-access externality problem have a large effect on both economic performance...... and CO2 emissions, while an additional CO2 regulation only has minor effects. The second-best solution achieved by only regulating open access reduces emissions by approximately 50% compared to current fisheries, with the exception of Iceland, which already has a well-developed fisheries management...

  5. FRACTIONAL DYNAMICS AT MULTIPLE TIMES

    OpenAIRE

    Meerschaert, Mark M.; Straka, Peter

    2012-01-01

    A continuous time random walk (CTRW) imposes a random waiting time between random particle jumps. CTRW limit densities solve a fractional Fokker-Planck equation, but since the CTRW limit is not Markovian, this is not sufficient to characterize the process. This paper applies continuum renewal theory to restore the Markov property on an expanded state space, and compute the joint CTRW limit density at multiple times.

  6. FRACTIONAL DYNAMICS AT MULTIPLE TIMES.

    Science.gov (United States)

    Meerschaert, Mark M; Straka, Peter

    2012-11-01

    A continuous time random walk (CTRW) imposes a random waiting time between random particle jumps. CTRW limit densities solve a fractional Fokker-Planck equation, but since the CTRW limit is not Markovian, this is not sufficient to characterize the process. This paper applies continuum renewal theory to restore the Markov property on an expanded state space, and compute the joint CTRW limit density at multiple times.

  7. Multiple grid methods for classical molecular dynamics.

    Science.gov (United States)

    Skeel, Robert D; Tezcan, Ismail; Hardy, David J

    2002-04-30

    Presented in the context of classical molecular mechanics and dynamics are multilevel summation methods for the fast calculation of energies/forces for pairwise interactions, which are based on the hierarchical interpolation of interaction potentials on multiple grids. The concepts and details underlying multigrid interpolation are described. For integration of molecular dynamics the use of different time steps for different interactions allows longer time steps for many of the interactions, and this can be combined with multiple grids in space. Comparison is made to the fast multipole method, and evidence is presented suggesting that for molecular simulations multigrid methods may be superior to the fast multipole method and other tree methods.

  8. Multiple dynamic transitions in nonequilibrium work fluctuations.

    Science.gov (United States)

    Noh, Jae Dong; Kwon, Chulan; Park, Hyunggyu

    2013-09-27

    The time-dependent work probability distribution function P(W) is investigated analytically for a diffusing particle trapped by an anisotropic harmonic potential and driven by a nonconservative drift force in two dimensions. We find that the exponential tail shape of P(W) characterizing rare-event probabilities undergoes a sequence of dynamic transitions in time. These remarkable locking-unlocking type transitions result from an intricate interplay between a rotational mode induced by the nonconservative force and an anisotropic decaying mode due to the conservative attractive force. We expect that most of the high-dimensional dynamical systems should exhibit similar multiple dynamic transitions.

  9. Basic dynamics at a multiple resonance

    International Nuclear Information System (INIS)

    Ferraz-Mello, S.; Yokoyama, T.

    The problem of multiple resonance is dealt with as it occurs in Celestial Mechanics and in non-linear Mechanics. In perturbation theory small divisors occur as a consequence of the fact that the flows in the phase space of the real system and the flows in the phase space of the so-called undisturbed system are not homeomorphic at all. Whatever the perturbation technique we adopt, the first step is to correct the topology of the undisturbed flows. It is shown that at a multiple resonance we are led to dynamical systems that are generally non-integrable. The basic representatives of these systems are the n-pendulums theta sup(:) sub(k) = σ sub(j)A sub(jk) sin theta sub(j). Multiple resonances are classified as syndetic or asyndetic following the eigenvalues of a quadratic form. Some degenerate cases are also presented. (Author) [pt

  10. Dynamics of bacterial gene regulation

    Science.gov (United States)

    Narang, Atul

    2009-03-01

    The phenomenon of diauxic growth is a classical problem of bacterial gene regulation. The most well studied example of this phenomenon is the glucose-lactose diauxie, which occurs because the expression of the lac operon is strongly repressed in the presence of glucose. This repression is often explained by appealing to molecular mechanisms such as cAMP activation and inducer exclusion. I will begin by analyzing data showing that these molecular mechanisms cannot explain the strong lac repression because they exert a relatively weak effect. I will then present a minimal model accounting only for enzyme induction and dilution, which yields strong repression despite the absence of catabolite repression and inducer exclusion. The model also explains the growth patterns observed in batch and continuous cultures of various bacterial strains and substrate mixtures. The talk will conclude with a discussion of the experimental evidence regarding positive feedback, the key component of the minimal model.

  11. Optimization of multi-response dynamic systems integrating multiple ...

    African Journals Online (AJOL)

    Optimization of multi-response dynamic systems integrating multiple regression and Taguchi's dynamic signal-to-noise ratio concept. ... Assuming a linear association exists between the response and signal variables, Taguchi offered a two-stage route for optimizing a dynamic system: maximize the dynamic signal-to noise ...

  12. Dynamic hydro-climatic networks in pristine and regulated rivers

    Science.gov (United States)

    Botter, G.; Basso, S.; Lazzaro, G.; Doulatyari, B.; Biswal, B.; Schirmer, M.; Rinaldo, A.

    2014-12-01

    Flow patterns observed at-a-station are the dynamical byproduct of a cascade of processes involving different compartments of the hydro-climatic network (e.g., climate, rainfall, soil, vegetation) that regulates the transformation of rainfall into streamflows. In complex branching rivers, flow regimes result from the heterogeneous arrangement around the stream network of multiple hydrologic cascades that simultaneously occur within distinct contributing areas. As such, flow regimes are seen as the integrated output of a complex "network of networks", which can be properly characterized by its degree of temporal variability and spatial heterogeneity. Hydrologic networks that generate river flow regimes are dynamic in nature. In pristine rivers, the time-variance naturally emerges at multiple timescales from climate variability (namely, seasonality and inter-annual fluctuations), implying that the magnitude (and the features) of the water flow between two nodes may be highly variable across different seasons and years. Conversely, the spatial distribution of river flow regimes within pristine rivers involves scale-dependent transport features, as well as regional climatic and soil use gradients, which in small and meso-scale catchments (A Human-impacted rivers, instead, constitute hybrid networks where observed spatio-temporal patterns are dominated by anthropogenic shifts, such as landscape alterations and river regulation. In regulated rivers, the magnitude and the features of water flows from node to node may change significantly through time due to damming and withdrawals. However, regulation may impact river regimes in a spatially heterogeneous manner (e.g. in localized river reaches), with a significant decrease of spatial correlations and network connectivity. Provided that the spatial and temporal dynamics of flow regimes in complex rivers may strongly impact important biotic processes involved in the river food web (e.g. biofilm and riparian vegetation

  13. Multiple upstream modules regulate zebrafish myf5 expression

    Directory of Open Access Journals (Sweden)

    Weng Chih-Wei

    2007-01-01

    Full Text Available Abstract Background Myf5 is one member of the basic helix-loop-helix family of transcription factors, and it functions as a myogenic factor that is important for the specification and differentiation of muscle cells. The expression of myf5 is somite- and stage-dependent during embryogenesis through a delicate regulation. However, this complex regulatory mechanism of myf5 is not clearly understood. Results We isolated a 156-kb bacterial artificial chromosome clone that includes an upstream 80-kb region and a downstream 70-kb region of zebrafish myf5 and generated a transgenic line carrying this 156-kb segment fused to a green fluorescent protein (GFP reporter gene. We find strong GFP expression in the most rostral somite and in the presomitic mesoderm during segmentation stages, similar to endogenous myf5 expression. Later, the GFP signals persist in caudal somites near the tail bud but are down-regulated in the older, rostral somites. During the pharyngula period, we detect GFP signals in pectoral fin buds, dorsal rostral myotomes, hypaxial myotomes, and inferior oblique and superior oblique muscles, a pattern that also corresponds well with endogenous myf5 transcripts. To characterize the specific upstream cis-elements that regulate this complex and dynamic expression pattern, we also generated several transgenic lines that harbor various lengths within the upstream 80-kb segment. We find that (1 the -80 kb/-9977 segment contains a fin and cranial muscle element and a notochord repressor; (2 the -9977/-6213 segment contains a strong repressive element that does not include the notochord-specific repressor; (3 the -6212/-2938 segment contains tissue-specific elements for bone and spinal cord; (4 the -2937/-291 segment contains an eye enhancer, and the -2937/-2457 segment is required for notochord and myocyte expression; and (5 the -290/-1 segment is responsible for basal transcription in somites and the presomitic mesoderm. Conclusion We suggest

  14. Analysis of the dynamics of reasoning using multiple representations

    NARCIS (Netherlands)

    Jonker, C.M.; Treur, J.

    2002-01-01

    This paper presents a formalisation and analysis method for the dynamics of a reasoning process in which multiple representations play a role. Dynamics of reasoning processes are described by reasoning traces consisting of sequences of reasoning states over time. Reasoning states have a

  15. Dynamic Characteristics Analysis and Stabilization of PV-Based Multiple Microgrid Clusters

    DEFF Research Database (Denmark)

    Zhao, Zhuoli; Yang, Ping; Wang, Yuewu

    2018-01-01

    As the penetration of PV generation increases, there is a growing operational demand on PV systems to participate in microgrid frequency regulation. It is expected that future distribution systems will consist of multiple microgrid clusters. However, interconnecting PV microgrids may lead to system...... interactions and instability. To date, no research work has been done to analyze the dynamic behavior and enhance the stability of microgrid clusters considering the dynamics of the PV primary sources and dc links. To fill this gap, this paper presents comprehensive modeling, analysis, and stabilization of PV......-based multiple microgrid clusters. A detailed small-signal model for PV-based microgrid clusters considering local adaptive dynamic droop control mechanism of the voltage-source PV system is developed. The complete dynamic model is then used to access and compare the dynamic characteristics of the single...

  16. Temporal dynamics and regulation of lake metabolism

    DEFF Research Database (Denmark)

    Stæhr, Peter Anton; Jensen, Kaj Sand

    2007-01-01

    and minima from fall to spring after broad-scale changes in irradiance, temperature, mixing depth, and biomass and growth rate of the algal community and concentrations of inorganic nutrients. Lake metabolism was annually balanced (mean GPP :R 1.04 in 2003 and 1.01 in 2004), with net autotrophy occurring......We studied temporal dynamics and regulation of oxygen metabolism in the upper mixed layer of a nutrientrich shallow Danish lake by continuous measurements of oxygen, irradiance, wind, and temperature and frequent measurements of algal chlorophyll, organic pools, and inorganic nutrients. Chlorophyll......, algal growth rate, and mean irradiance (Emean) in the mixed surface layer were calculated daily from continuous measurements of irradiance and temperature with depth. There were three to four distinct maxima in gross primary production (GPP) and community respiration (R) during the summer season...

  17. Dynamic processes in emotion regulation choice.

    Science.gov (United States)

    Murphy, Jonathan W; Young, Michael A

    2017-12-27

    Because emotion regulation (ER) processes operate over time, they potentially change the context in which subsequent ER processes occur. To test this proposal, fifty-two healthy participants completed the ER choice task. Thirty standardized low- and high-intensity negative images were used to generate different emotional contexts in which participants selected between distraction or reappraisal strategies to decrease the intensity of their negative emotion. Participants then implemented their selected strategy and rated their negative emotion. Using a dynamic perspective, we examined as predictors of ER strategy choice, in addition to current stimulus intensity, several contextual factors from the immediately preceding trial: preceding stimulus intensity and strategy choice, and the intensity of negative affect following the previous strategy implementation and thus preceding the current trial. Results replicated earlier findings that participants are more likely to choose distraction for high-intensity images. Extending earlier findings, selecting reappraisal in the preceding trial and greater negative affect preceding the current trial were associated with lower odds of choosing distraction. The lack of significant interactions among the current and preceding trial factors suggests that these effects on ER choice were direct and not through moderating the effect of current stimulus intensity. These findings support dynamic theories of ER.

  18. NLR-Dependent Regulation of Inflammation in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Marjan Gharagozloo

    2018-01-01

    Full Text Available Multiple sclerosis (MS is an autoimmune disease of the central nervous system (CNS associated with inappropriate activation of lymphocytes, hyperinflammatory responses, demyelination, and neuronal damage. In the past decade, a number of biological immunomodulators have been developed that suppress the peripheral immune responses and slow down the progression of the disease. However, once the inflammation of the CNS has commenced, it can cause serious permanent neuronal damage. Therefore, there is a need for developing novel therapeutic approaches that control and regulate inflammatory responses within the CNS. Nucleotide-binding oligomerization domain (NOD-like receptors (NLRs are intracellular regulators of inflammation expressed by many cell types within the CNS. They redirect multiple signaling pathways initiated by pathogens and molecules released by injured tissues. NLR family members include positive regulators of inflammation, such as NLRP3 and NLRC4 and anti-inflammatory NLRs, such as NLRX1 and NLRP12. They exert immunomodulatory effect at the level of peripheral immune responses, including antigen recognition and lymphocyte activation and differentiation. Also, NLRs regulate tissue inflammatory responses. Understanding the molecular mechanisms that are placed at the crossroad of innate and adaptive immune responses, such as NLR-dependent pathways, could lead to the discovery of new therapeutic targets. In this review, we provide a summary of the role of NLRs in the pathogenesis of MS. We also summarize how anti-inflammatory NLRs regulate the immune response within the CNS. Finally, we speculate the therapeutic potential of targeting NLRs in MS.

  19. AMBIDEXTER Dynamics and Self-Regulation Capability

    International Nuclear Information System (INIS)

    Oh, Se Kee; Lee, Young Joon; Ham, Tae Kyu; Seo, Myung Hwan; Hong, Sung Taek; Kwon, Tae An

    2009-01-01

    Safety-related events in a nuclear reactor system are mostly incurred by sudden imbalance between their heat source and sink behaviors. Controllability and resiliency are assessed if the system be safely recoverable from the imbalance. Inherent safety characteristics of the reactor should be an ideal design philosophy in this aspect. The AMBIDEXTER safety design was explored with maximum reliance on counteractive responses by the system itself. As for the realization, negative reactivity feedback and fail-safe criteria are the fundamental considerations. Details of how to implement them in the design can be found in the paper accompanied. the reactor and the primary heat exchanger are integrated into a closed loop in the vessel. The fuel salt flows downwardly in the outer core region, gains fission heat and then, rises upwardly through the central inner core region where resonance absorbers face better conversion chance. In the primary heat exchanger, heat transfer between the tube-side fuel salt and the shell-side coolant salt is made. For chemical processing, part of the fuel salt flow is discharged from the heat exchanger and returns to the reactor through bypass line. This paper examines the dynamic performances of the AMBIDEXTER reactor system to investigate the range of its self-regulation capability and safety impacts

  20. Myosin II dynamics are regulated by tension in intercalating cells.

    Science.gov (United States)

    Fernandez-Gonzalez, Rodrigo; Simoes, Sérgio de Matos; Röper, Jens-Christian; Eaton, Suzanne; Zallen, Jennifer A

    2009-11-01

    Axis elongation in Drosophila occurs through polarized cell rearrangements driven by actomyosin contractility. Myosin II promotes neighbor exchange through the contraction of single cell boundaries, while the contraction of myosin II structures spanning multiple pairs of cells leads to rosette formation. Here we show that multicellular actomyosin cables form at a higher frequency than expected by chance, indicating that cable assembly is an active process. Multicellular cables are sites of increased mechanical tension as measured by laser ablation. Fluorescence recovery after photobleaching experiments show that myosin II is stabilized at the cortex in regions of increased tension. Myosin II is recruited in response to an ectopic force and relieving tension leads to a rapid loss of myosin, indicating that tension is necessary and sufficient for cortical myosin localization. These results demonstrate that myosin II dynamics are regulated by tension in a positive feedback loop that leads to multicellular actomyosin cable formation and efficient tissue elongation.

  1. Dynamic Initiation and Propagation of Multiple Cracks in Brittle Materials

    Directory of Open Access Journals (Sweden)

    Xiaodan Ren

    2013-07-01

    Full Text Available Brittle materials such as rock and ceramic usually exhibit apparent increases of strength and toughness when subjected to dynamic loading. The reasons for this phenomenon are not yet well understood, although a number of hypotheses have been proposed. Based on dynamic fracture mechanics, the present work offers an alternate insight into the dynamic behaviors of brittle materials. Firstly, a single crack subjected to stress wave excitations is investigated to obtain the dynamic crack-tip stress field and the dynamic stress intensity factor. Second, based on the analysis of dynamic stress intensity factor, the fracture initiation sizes and crack size distribution under different loading rates are obtained, and the power law with the exponent of −2/3 is derived to describe the fracture initiation size. Third, with the help of the energy balance concept, the dynamic increase of material strength is directly derived based on the proposed multiple crack evolving criterion. Finally, the model prediction is compared with the dynamic impact experiments, and the model results agree well with the experimentally measured dynamic increasing factor (DIF.

  2. Multiple dynamical time-scales in networks with hierarchically ...

    Indian Academy of Sciences (India)

    Multiple dynamical time-scales in networks with hierarchically nested modular organization ... http://www.ias.ac.in/article/fulltext/pram/077/05/0833-0842 ... Many natural and engineered complex networks have intricate mesoscopic organization, e.g., the clustering of the constituent nodes into several communities or ...

  3. Criteria for stability of linear dynamical systems with multiple delays ...

    African Journals Online (AJOL)

    In this study we considered a linear Dynamical system with multiple delays and find suitable conditions on the systems parameters such that for a given initial function, we can define a mapping in a carefully chosen complete metric space on which the mapping has a unique fixed point. An asymptotic stability theory for the ...

  4. Dynamic pricing with multiple products and partially specified demand distribution

    NARCIS (Netherlands)

    den Boer, A.V.

    We study a dynamic pricing problem with multiple products and infinite inventories. The demand for these products depends on the selling prices and on parameters unknown to the seller. Their value can be learned from accumulating sales data using statistical estimation techniques. The quality of the

  5. The central mechanisms of secretin in regulating multiple behaviors

    Directory of Open Access Journals (Sweden)

    Li eZhang

    2014-05-01

    Full Text Available Secretin (SCT was firstly discovered as a gut peptide hormone in stimulating pancreatic secretion, while its novel neuropeptide role has drawn substantial research interests in recent years. SCT and its receptor (SCTR are widely expressed in different brain regions, where they exert multiple cellular functions including neurotransmission, gene expression regulation, neurogenesis and neural protection. As all these neural functions ultimately can affect behaviors, it is hypothesized that SCT controls multiple behavioral paradigms. Current findings support this hypothesis as SCT-SCTR axis participates in modulating social interaction, spatial learning, water and food intake, motor coordination and motor learning behaviors. This mini-review focuses on various aspects of SCT and SCTR in hippocampus, hypothalamus and cerebellum including distribution profiles, cellular functions and behavioral phenotypes to elucidate the link between cellular mechanisms and behavioral control.

  6. Multiple roles for the actin cytoskeleton during regulated exocytosis

    Science.gov (United States)

    Porat-Shliom, Natalie; Milberg, Oleg; Masedunskas, Andrius; Weigert, Roberto

    2014-01-01

    Regulated exocytosis is the main mechanism utilized by specialized secretory cells to deliver molecules to the cell surface by virtue of membranous containers (i.e. secretory vesicles). The process involves a series of highly coordinated and sequential steps, which include the biogenesis of the vesicles, their delivery to the cell periphery, their fusion with the plasma membrane and the release of their content into the extracellular space. Each of these steps is regulated by the actin cytoskeleton. In this review, we summarize the current knowledge regarding the involvement of actin and its associated molecules during each of the exocytic steps in vertebrates, and suggest that the overall role of the actin cytoskeleton during regulated exocytosis is linked to the architecture and the physiology of the secretory cells under examination. Specifically, in neurons, neuroendocrine, endocrine, and hematopoietic cells, which contain small secretory vesicles that undergo rapid exocytosis (on the order of milliseconds), the actin cytoskeleton plays a role in pre-fusion events, where it acts primarily as a functional barrier and facilitates docking. In exocrine and other secretory cells, which contain large secretory vesicles that undergo slow exocytosis (seconds to minutes), the actin cytoskeleton plays a role in post-fusion events, where it regulates the dynamics of the fusion pore, facilitates the integration of the vesicles into the plasma membrane, provides structural support, and promotes the expulsion of large cargo molecules. PMID:22986507

  7. Dynamic regulation of glucocorticoid signalling in health and disease

    OpenAIRE

    Biddie, Simon C.; Conway-Campbell, Becky L.; Lightman, Stafford L.

    2011-01-01

    Activation of the glucocorticoid receptor (GR) by endogenous and synthetic glucocorticoids regulates hundreds of genes to control regulatory networks in development, metabolism, cognition and inflammation. Elucidation of the mechanisms that regulate glucocorticoid action has highlighted the dynamic nature of hormone signalling and provides novel insights into genomic glucocorticoid actions. The major factors that regulate GR function include chromatin structure, epigenetics, genetic variation...

  8. Regulation of multiple carbon monoxide consumption pathways in anaerobic bacteria

    Directory of Open Access Journals (Sweden)

    Stephen M Techtmann

    2011-07-01

    Full Text Available Carbon monoxide (CO, well known as a toxic gas, is increasingly recognized as a key metabolite and signaling molecule. Microbial utilization of CO is quite common, evidenced by the rapid escalation in description of new species of CO-utilizing bacteria and archaea. Carbon monoxide dehydrogenase (CODH, the protein complex that enables anaerobic CO utilization has been well-characterized from an increasing number of microorganisms, however the regulation of multiple CO-related gene clusters in single isolates remains unexplored. Many species are extroraordinarily resistant to high CO concentrations, thiriving under pure CO at more than one atmosphere. We hypothesized that, in strains that can grow exclusively on CO, both carbon acquisition via the CODH/Acetyl CoA synthase complex and energy conservation via a CODH-linked hydrogenase must be differentially regulated in response to the availability of CO. The CO-sensing transcriptional activator, CooA is present in most CO-oxidizing bacteria. Here we present a genomic and phylogenetic survey of CODH operons and cooA genes found in CooA-containing bacteria. Two distinct groups of CooA homologs were found: One clade (CooA-1 is found in the majority of CooA containing bacteria, whereas the other clade (CooA-2 is found only in genomes that encode multiple CODH clusters, suggesting that the CooA-2 might be important for cross-regulation of competing CODH operons. Recombinant CooA-1 and CooA-2 regulators from the prototypical CO-utilizing bacterium Carboxydothermus hydrogenoformans were purified, and promoter binding analyses revealed that CooA-1 specifically regulates the hydrogenase-linked CODH, whereas CooA-2 is able to regulate both the hydrogenase-linked CODH and the CODH/ACS operons. These studies point to the ability of dual CooA homologs to partition CO into divergent CO-utilizing pathways resulting in efficient consumption of a single limiting growth substrate available across a wide range of

  9. Neural Computations in a Dynamical System with Multiple Time Scales

    Directory of Open Access Journals (Sweden)

    Yuanyuan Mi

    2016-09-01

    Full Text Available Neural systems display rich short-term dynamics at various levels, e.g., spike-frequencyadaptation (SFA at single neurons, and short-term facilitation (STF and depression (STDat neuronal synapses. These dynamical features typically covers a broad range of time scalesand exhibit large diversity in different brain regions. It remains unclear what the computationalbenefit for the brain to have such variability in short-term dynamics is. In this study, we proposethat the brain can exploit such dynamical features to implement multiple seemingly contradictorycomputations in a single neural circuit. To demonstrate this idea, we use continuous attractorneural network (CANN as a working model and include STF, SFA and STD with increasing timeconstants in their dynamics. Three computational tasks are considered, which are persistent activity,adaptation, and anticipative tracking. These tasks require conflicting neural mechanisms, andhence cannot be implemented by a single dynamical feature or any combination with similar timeconstants. However, with properly coordinated STF, SFA and STD, we show that the network isable to implement the three computational tasks concurrently. We hope this study will shed lighton the understanding of how the brain orchestrates its rich dynamics at various levels to realizediverse cognitive functions.

  10. Computer studies of multiple-quantum spin dynamics

    International Nuclear Information System (INIS)

    Murdoch, J.B.

    1982-11-01

    The excitation and detection of multiple-quantum (MQ) transitions in Fourier transform NMR spectroscopy is an interesting problem in the quantum mechanical dynamics of spin systems as well as an important new technique for investigation of molecular structure. In particular, multiple-quantum spectroscopy can be used to simplify overly complex spectra or to separate the various interactions between a nucleus and its environment. The emphasis of this work is on computer simulation of spin-system evolution to better relate theory and experiment

  11. Computer studies of multiple-quantum spin dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Murdoch, J.B.

    1982-11-01

    The excitation and detection of multiple-quantum (MQ) transitions in Fourier transform NMR spectroscopy is an interesting problem in the quantum mechanical dynamics of spin systems as well as an important new technique for investigation of molecular structure. In particular, multiple-quantum spectroscopy can be used to simplify overly complex spectra or to separate the various interactions between a nucleus and its environment. The emphasis of this work is on computer simulation of spin-system evolution to better relate theory and experiment.

  12. Exoplanetary System Dynamics: Planetary Multiplicity and Mass Effects

    Science.gov (United States)

    Isoe, Mari; Kokubo, Eiichiro; Turner, Edwin

    2015-12-01

    Recently numerous systems consisting of multiple exoplanets have been discovered. Using a dataset of 375 systems (500 planets) discovered by the radial velocity method and 365 systems (899 planets) containing planet candidates found by the Kepler Mission, we investigate the dependence of the dynamical structure of planetary systems on their multiplicity and the masses of the member planets. We classify the planetary system by three parameters: planetary multiplicity, planetary mass, and the evolutionary stage of the central star. We normalize planetary masses by the mass of the central star and divide the planets into small and large categories by a cut at $10^{-4}$. The central star is classified into main-sequence or giant according to its evolutionary stage. We focus on the angular momentum deficit (AMD) of the systems and the orbital separation between adjacent planets normalized by their Hill radii. We find that in all categories the system AMD decreases with increasing multiplicity. This suggests that in order for multiple systems to be stable, each planet's orbit must be relatively circular. In addition, we find that the distribution of orbital eccentricities of the massive planets and low-mass planets differs. In particular, only high-mass planets have eccentricities larger than 0.4. In the low-mass systems around main sequence stars, we find that the orbital separation decreases with increasing multiplicity. In addition, the orbital separation around main-sequence stars is wider than that around giants. Furthermore, the minimum orbital separation is about 6.4 for non-resonant pairs. This paper presents the statistical properties of the dynamical structure of multiple planetary systems and discusses their formation.

  13. Experimentation of Eigenvector Dynamics in a Multiple Input Multiple Output Channel in the 5GHz Band

    DEFF Research Database (Denmark)

    Brown, Tim; Eggers, Patrick Claus F.; Katz, Marcos

    2005-01-01

    Much research has been carried out on the production of both physical and non physical Multiple Input Multiple Output channel models with regard to increased channel capacity as well as analysis of eigenvalues through the use of singular value decomposition. Little attention has been paid...... to the analysis of vector dynamics in terms of how the state of eigenvectors will change as a mobile is moving through a changing physical environment. This is important in terms of being able to track the orthogonal eigenmodes at system level, while also relieving the burden of tracking of the full channel...

  14. Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation

    Science.gov (United States)

    Andlauer, Till F. M.; Buck, Dorothea; Antony, Gisela; Bayas, Antonios; Bechmann, Lukas; Berthele, Achim; Chan, Andrew; Gasperi, Christiane; Gold, Ralf; Graetz, Christiane; Haas, Jürgen; Hecker, Michael; Infante-Duarte, Carmen; Knop, Matthias; Kümpfel, Tania; Limmroth, Volker; Linker, Ralf A.; Loleit, Verena; Luessi, Felix; Meuth, Sven G.; Mühlau, Mark; Nischwitz, Sandra; Paul, Friedemann; Pütz, Michael; Ruck, Tobias; Salmen, Anke; Stangel, Martin; Stellmann, Jan-Patrick; Stürner, Klarissa H.; Tackenberg, Björn; Then Bergh, Florian; Tumani, Hayrettin; Warnke, Clemens; Weber, Frank; Wiendl, Heinz; Wildemann, Brigitte; Zettl, Uwe K.; Ziemann, Ulf; Zipp, Frauke; Arloth, Janine; Weber, Peter; Radivojkov-Blagojevic, Milena; Scheinhardt, Markus O.; Dankowski, Theresa; Bettecken, Thomas; Lichtner, Peter; Czamara, Darina; Carrillo-Roa, Tania; Binder, Elisabeth B.; Berger, Klaus; Bertram, Lars; Franke, Andre; Gieger, Christian; Herms, Stefan; Homuth, Georg; Ising, Marcus; Jöckel, Karl-Heinz; Kacprowski, Tim; Kloiber, Stefan; Laudes, Matthias; Lieb, Wolfgang; Lill, Christina M.; Lucae, Susanne; Meitinger, Thomas; Moebus, Susanne; Müller-Nurasyid, Martina; Nöthen, Markus M.; Petersmann, Astrid; Rawal, Rajesh; Schminke, Ulf; Strauch, Konstantin; Völzke, Henry; Waldenberger, Melanie; Wellmann, Jürgen; Porcu, Eleonora; Mulas, Antonella; Pitzalis, Maristella; Sidore, Carlo; Zara, Ilenia; Cucca, Francesco; Zoledziewska, Magdalena; Ziegler, Andreas; Hemmer, Bernhard; Müller-Myhsok, Bertram

    2016-01-01

    We conducted a genome-wide association study (GWAS) on multiple sclerosis (MS) susceptibility in German cohorts with 4888 cases and 10,395 controls. In addition to associations within the major histocompatibility complex (MHC) region, 15 non-MHC loci reached genome-wide significance. Four of these loci are novel MS susceptibility loci. They map to the genes L3MBTL3, MAZ, ERG, and SHMT1. The lead variant at SHMT1 was replicated in an independent Sardinian cohort. Products of the genes L3MBTL3, MAZ, and ERG play important roles in immune cell regulation. SHMT1 encodes a serine hydroxymethyltransferase catalyzing the transfer of a carbon unit to the folate cycle. This reaction is required for regulation of methylation homeostasis, which is important for establishment and maintenance of epigenetic signatures. Our GWAS approach in a defined population with limited genetic substructure detected associations not found in larger, more heterogeneous cohorts, thus providing new clues regarding MS pathogenesis. PMID:27386562

  15. Regulation of memory accuracy with multiple answers: the plurality option.

    Science.gov (United States)

    Luna, Karlos; Higham, Philip A; Martín-Luengo, Beatriz

    2011-06-01

    We report two experiments that investigated the regulation of memory accuracy with a new regulatory mechanism: the plurality option. This mechanism is closely related to the grain-size option but involves control over the number of alternatives contained in an answer rather than the quantitative boundaries of a single answer. Participants were presented with a slideshow depicting a robbery (Experiment 1) or a murder (Experiment 2), and their memory was tested with five-alternative multiple-choice questions. For each question, participants were asked to generate two answers: a single answer consisting of one alternative and a plural answer consisting of the single answer and two other alternatives. Each answer was rated for confidence (Experiment 1) or for the likelihood of being correct (Experiment 2), and one of the answers was selected for reporting. Results showed that participants used the plurality option to regulate accuracy, selecting single answers when their accuracy and confidence were high, but opting for plural answers when they were low. Although accuracy was higher for selected plural than for selected single answers, the opposite pattern was evident for confidence or likelihood ratings. This dissociation between confidence and accuracy for selected answers was the result of marked overconfidence in single answers coupled with underconfidence in plural answers. We hypothesize that these results can be attributed to overly dichotomous metacognitive beliefs about personal knowledge states that cause subjective confidence to be extreme.

  16. Multiple shooting shadowing for sensitivity analysis of chaotic dynamical systems

    Science.gov (United States)

    Blonigan, Patrick J.; Wang, Qiqi

    2018-02-01

    Sensitivity analysis methods are important tools for research and design with simulations. Many important simulations exhibit chaotic dynamics, including scale-resolving turbulent fluid flow simulations. Unfortunately, conventional sensitivity analysis methods are unable to compute useful gradient information for long-time-averaged quantities in chaotic dynamical systems. Sensitivity analysis with least squares shadowing (LSS) can compute useful gradient information for a number of chaotic systems, including simulations of chaotic vortex shedding and homogeneous isotropic turbulence. However, this gradient information comes at a very high computational cost. This paper presents multiple shooting shadowing (MSS), a more computationally efficient shadowing approach than the original LSS approach. Through an analysis of the convergence rate of MSS, it is shown that MSS can have lower memory usage and run time than LSS.

  17. Dynamic knowledge management from multiple sources in crowdsourcing environments

    Science.gov (United States)

    Kim, Mucheol; Rho, Seungmin

    2015-10-01

    Due to the spread of smart devices and the development of network technology, a large number of people can now easily utilize the web for acquiring information and various services. Further, collective intelligence has emerged as a core player in the evolution of technology in web 2.0 generation. It means that people who are interested in a specific domain of knowledge can not only make use of the information, but they can also participate in the knowledge production processes. Since a large volume of knowledge is produced by multiple contributors, it is important to integrate and manage knowledge efficiently. In this paper, we propose a social tagging-based dynamic knowledge management system in crowdsourcing environments. The approach here is to categorize and package knowledge from multiple sources, in such a way that it easily links to target knowledge.

  18. Multiple-charge beam dynamics in an ion linac

    Directory of Open Access Journals (Sweden)

    P. N . Ostroumov

    2000-03-01

    Full Text Available An advanced facility for the production of nuclei far from stability could be based on a high-power driver accelerator providing ion beams over the full mass range from protons to uranium. A beam power of several hundred kilowatts is highly desirable for this application. At present, however, the beam power available for the heavier ions would be limited by ion source capabilities. A simple and cost-effective method to enhance the available beam current would be to accelerate multiple charge states through a superconducting ion linac. This paper presents results of numerical simulation of multiple charge state beams through a 1.3 GeV ion linac, the design of which is based on current state-of-the-art superconducting elements. The dynamics of multiple charge state beams are detailed, including the effects of possible errors in rf field parameters and misalignments of transverse focusing elements. The results indicate that operation with multiple charge state beams is not only feasible but straightforward and can increase the beam current by a factor of 3 or more.

  19. Dynamical Analysis of bantam-Regulated Drosophila Circadian Rhythm Model

    Science.gov (United States)

    Li, Ying; Liu, Zengrong

    MicroRNAs (miRNAs) interact with 3‧untranslated region (UTR) elements of target genes to regulate mRNA stability or translation, and play a crucial role in regulating many different biological processes. bantam, a conserved miRNA, is involved in several functions, such as regulating Drosophila growth and circadian rhythm. Recently, it has been discovered that bantam plays a crucial role in the core circadian pacemaker. In this paper, based on experimental observations, a detailed dynamical model of bantam-regulated circadian clock system is developed to show the post-transcriptional behaviors in the modulation of Drosophila circadian rhythm, in which the regulation of bantam is incorporated into a classical model. The dynamical behaviors of the model are consistent with the experimental observations, which shows that bantam is an important regulator of Drosophila circadian rhythm. The sensitivity analysis of parameters demonstrates that with the regulation of bantam the system is more sensitive to perturbations, indicating that bantam regulation makes it easier for the organism to modulate its period against the environmental perturbations. The effectiveness in rescuing locomotor activity rhythms of mutated flies shows that bantam is necessary for strong and sustained rhythms. In addition, the biological mechanisms of bantam regulation are analyzed, which may help us more clearly understand Drosophila circadian rhythm regulated by other miRNAs.

  20. The dynamic landscape of gene regulation during Bombyx mori oogenesis.

    Science.gov (United States)

    Zhang, Qiang; Sun, Wei; Sun, Bang-Yong; Xiao, Yang; Zhang, Ze

    2017-09-11

    Oogenesis in the domestic silkworm (Bombyx mori) is a complex process involving previtellogenesis, vitellogenesis and choriogenesis. During this process, follicles show drastic morphological and physiological changes. However, the genome-wide regulatory profiles of gene expression during oogenesis remain to be determined. In this study, we obtained time-series transcriptome data and used these data to reveal the dynamic landscape of gene regulation during oogenesis. A total of 1932 genes were identified to be differentially expressed among different stages, most of which occurred during the transition from late vitellogenesis to early choriogenesis. Using weighted gene co-expression network analysis, we identified six stage-specific gene modules that correspond to multiple regulatory pathways. Strikingly, the biosynthesis pathway of the molting hormone 20-hydroxyecdysone (20E) was enriched in one of the modules. Further analysis showed that the ecdysteroid 20-hydroxylase gene (CYP314A1) of steroidgenesis genes was mainly expressed in previtellogenesis and early vitellogenesis. However, the 20E-inactivated genes, particularly the ecdysteroid 26-hydroxylase encoding gene (Cyp18a1), were highly expressed in late vitellogenesis. These distinct expression patterns between 20E synthesis and catabolism-related genes might ensure the rapid decline of the hormone titer at the transition point from vitellogenesis to choriogenesis. In addition, we compared landscapes of gene regulation between silkworm (Lepidoptera) and fruit fly (Diptera) oogeneses. Our results show that there is some consensus in the modules of gene co-expression during oogenesis in these insects. The data presented in this study provide new insights into the regulatory mechanisms underlying oogenesis in insects with polytrophic meroistic ovaries. The results also provide clues for further investigating the roles of epigenetic reconfiguration and circadian rhythm in insect oogenesis.

  1. Kinematics and dynamics of robotic systems with multiple closed loops

    Science.gov (United States)

    Zhang, Chang-De

    The kinematics and dynamics of robotic systems with multiple closed loops, such as Stewart platforms, walking machines, and hybrid manipulators, are studied. In the study of kinematics, focus is on the closed-form solutions of the forward position analysis of different parallel systems. A closed-form solution means that the solution is expressed as a polynomial in one variable. If the order of the polynomial is less than or equal to four, the solution has analytical closed-form. First, the conditions of obtaining analytical closed-form solutions are studied. For a Stewart platform, the condition is found to be that one rotational degree of freedom of the output link is decoupled from the other five. Based on this condition, a class of Stewart platforms which has analytical closed-form solution is formulated. Conditions of analytical closed-form solution for other parallel systems are also studied. Closed-form solutions of forward kinematics for walking machines and multi-fingered grippers are then studied. For a parallel system with three three-degree-of-freedom subchains, there are 84 possible ways to select six independent joints among nine joints. These 84 ways can be classified into three categories: Category 3:3:0, Category 3:2:1, and Category 2:2:2. It is shown that the first category has no solutions; the solutions of the second category have analytical closed-form; and the solutions of the last category are higher order polynomials. The study is then extended to a nearly general Stewart platform. The solution is a 20th order polynomial and the Stewart platform has a maximum of 40 possible configurations. Also, the study is extended to a new class of hybrid manipulators which consists of two serially connected parallel mechanisms. In the study of dynamics, a computationally efficient method for inverse dynamics of manipulators based on the virtual work principle is developed. Although this method is comparable with the recursive Newton-Euler method for

  2. Dynamic models for problems of species occurrence with multiple states

    Science.gov (United States)

    MacKenzie, D.I.; Nichols, J.D.; Seamans, M.E.; Gutierrez, R.J.

    2009-01-01

    Recent extensions of occupancy modeling have focused not only on the distribution of species over space, but also on additional state variables (e.g., reproducing or not, with or without disease organisms, relative abundance categories) that provide extra information about occupied sites. These biologist-driven extensions are characterized by ambiguity in both species presence and correct state classification, caused by imperfect detection. We first show the relationships between independently published approaches to the modeling of multistate occupancy. We then extend the pattern-based modeling to the case of sampling over multiple seasons or years in order to estimate state transition probabilities associated with system dynamics. The methodology and its potential for addressing relevant ecological questions are demonstrated using both maximum likelihood (occupancy and successful reproduction dynamics of California Spotted Owl) and Markov chain Monte Carlo estimation approaches (changes in relative abundance of green frogs in Maryland). Just as multistate capture?recapture modeling has revolutionized the study of individual marked animals, we believe that multistate occupancy modeling will dramatically increase our ability to address interesting questions about ecological processes underlying population-level dynamics.

  3. Modeling species occurrence dynamics with multiple states and imperfect detection

    Science.gov (United States)

    MacKenzie, D.I.; Nichols, J.D.; Seamans, M.E.; Gutierrez, R.J.

    2009-01-01

    Recent extensions of occupancy modeling have focused not only on the distribution of species over space, but also on additional state variables (e.g., reproducing or not, with or without disease organisms, relative abundance categories) that provide extra information about occupied sites. These biologist-driven extensions are characterized by ambiguity in both species presence and correct state classification, caused by imperfect detection. We first show the relationships between independently published approaches to the modeling of multistate occupancy. We then extend the pattern-based modeling to the case of sampling over multiple seasons or years in order to estimate state transition probabilities associated with system dynamics. The methodology and its potential for addressing relevant ecological questions are demonstrated using both maximum likelihood (occupancy and successful reproduction dynamics of California Spotted Owl) and Markov chain Monte Carlo estimation approaches (changes in relative abundance of green frogs in Maryland). Just as multistate capture-recapture modeling has revolutionized the study of individual marked animals, we believe that multistate occupancy modeling will dramatically increase our ability to address interesting questions about ecological processes underlying population-level dynamics. ?? 2009 by the Ecological Society of America.

  4. Dynamic response of multiple nanobeam system under a moving nanoparticle

    Directory of Open Access Journals (Sweden)

    Shahrokh Hosseini Hashemi

    2018-03-01

    Full Text Available In this article, nonlocal continuum based model of multiple nanobeam system (MNBS under a moving nanoparticle is investigated using Eringen’s nonlocal theory. Beam layers are assumed to be coupled by winkler elastic medium and the nonlocal Euler-Bernoulli beam theory is used to model each layer of beam. The Hamilton’s principle, Eigen function technique and the Laplace transform method are employed to solve the governing equations. Analytical solutions of the transverse displacements for MNBs with simply supported boundary condition are presented for double layered and three layered MNBSs. For higher number of layers, the governing set of equations is solved numerically and the results are presented. This study shows that small-scale parameter has a significant effect on dynamic response of MNBS under a moving nanoparticle. Sensitivity of dynamical deflection to variation of nonlocal parameter, stiffness of Winkler elastic medium and number of nanobeams are presented in nondimensional form for each layer. Keywords: Dynamic response, Analytical solution, Moving particle, Nanobeam, Multi-layered nanobeam

  5. Genome-wide screens for gene products regulating lipid droplet dynamics.

    Science.gov (United States)

    Fei, Weihua; Yang, Hongyuan

    2012-01-01

    Lipid droplets (LDs) are emerging as dynamic cellular organelles that play a key role in lipid and membrane homeostasis. Abnormal lipid droplet dynamics are associated with the pathophysiology of many metabolic diseases, such as obesity, diabetes, atherosclerosis, fatty liver, and even cancer. Understanding the molecular mechanisms governing the dynamics of LDs, namely, their biogenesis, growth, maintenance, and degradation, will not only shed light on the cellular functions of LDs, but also provide additional clues to treatment of metabolic diseases. Genome-wide screen is a powerful approach to identify genetic factors that regulate lipid droplet dynamics. Here, we summarize recent genome-wide studies using yeast and Drosophila cells to understand the cellular dynamics of LDs. The results suggest that the genome-wide screens should be carried out in multiple organisms or cells, and using different nutritional conditions. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Cinnamon polyphenols regulate multiple metabolic pathways involved in intestinal lipid metabolism of primary small intestinal enterocytes

    Science.gov (United States)

    Increasing evidence suggests that dietary factors may affect the expression of multiple genes and signaling pathways including those that regulate intestinal lipoprotein metabolism. The small intestine is actively involved in the regulation of dietary lipid absorption, intracellular transport and me...

  7. Cytoskeletal Network Morphology Regulates Intracellular Transport Dynamics

    Science.gov (United States)

    Ando, David; Korabel, Nickolay; Huang, Kerwyn Casey; Gopinathan, Ajay

    2015-01-01

    Intracellular transport is essential for maintaining proper cellular function in most eukaryotic cells, with perturbations in active transport resulting in several types of disease. Efficient delivery of critical cargos to specific locations is accomplished through a combination of passive diffusion and active transport by molecular motors that ballistically move along a network of cytoskeletal filaments. Although motor-based transport is known to be necessary to overcome cytoplasmic crowding and the limited range of diffusion within reasonable timescales, the topological features of the cytoskeletal network that regulate transport efficiency and robustness have not been established. Using a continuum diffusion model, we observed that the time required for cellular transport was minimized when the network was localized near the nucleus. In simulations that explicitly incorporated network spatial architectures, total filament mass was the primary driver of network transit times. However, filament traps that redirect cargo back to the nucleus caused large variations in network transport. Filament polarity was more important than filament orientation in reducing average transit times, and transport properties were optimized in networks with intermediate motor on and off rates. Our results provide important insights into the functional constraints on intracellular transport under which cells have evolved cytoskeletal structures, and have potential applications for enhancing reactions in biomimetic systems through rational transport network design. PMID:26488648

  8. Cytoskeletal Network Morphology Regulates Intracellular Transport Dynamics.

    Science.gov (United States)

    Ando, David; Korabel, Nickolay; Huang, Kerwyn Casey; Gopinathan, Ajay

    2015-10-20

    Intracellular transport is essential for maintaining proper cellular function in most eukaryotic cells, with perturbations in active transport resulting in several types of disease. Efficient delivery of critical cargos to specific locations is accomplished through a combination of passive diffusion and active transport by molecular motors that ballistically move along a network of cytoskeletal filaments. Although motor-based transport is known to be necessary to overcome cytoplasmic crowding and the limited range of diffusion within reasonable timescales, the topological features of the cytoskeletal network that regulate transport efficiency and robustness have not been established. Using a continuum diffusion model, we observed that the time required for cellular transport was minimized when the network was localized near the nucleus. In simulations that explicitly incorporated network spatial architectures, total filament mass was the primary driver of network transit times. However, filament traps that redirect cargo back to the nucleus caused large variations in network transport. Filament polarity was more important than filament orientation in reducing average transit times, and transport properties were optimized in networks with intermediate motor on and off rates. Our results provide important insights into the functional constraints on intracellular transport under which cells have evolved cytoskeletal structures, and have potential applications for enhancing reactions in biomimetic systems through rational transport network design. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  9. Regulation of ribonucleotide reductase by Spd1 involves multiple mechanisms

    DEFF Research Database (Denmark)

    Nestoras, Konstantinos; Mohammed, Asma Hadi; Schreurs, Ann-Sofie

    2010-01-01

    The correct levels of deoxyribonucleotide triphosphates and their relative abundance are important to maintain genomic integrity. Ribonucleotide reductase (RNR) regulation is complex and multifaceted. RNR is regulated allosterically by two nucleotide-binding sites, by transcriptional control, and...

  10. Integrin-linked kinase regulates interphase and mitotic microtubule dynamics.

    Directory of Open Access Journals (Sweden)

    Simin Lim

    Full Text Available Integrin-linked kinase (ILK localizes to both focal adhesions and centrosomes in distinct multiprotein complexes. Its dual function as a kinase and scaffolding protein has been well characterized at focal adhesions, where it regulates integrin-mediated cell adhesion, spreading, migration and signaling. At the centrosomes, ILK regulates mitotic spindle organization and centrosome clustering. Our previous study showed various spindle defects after ILK knockdown or inhibition that suggested alteration in microtubule dynamics. Since ILK expression is frequently elevated in many cancer types, we investigated the effects of ILK overexpression on microtubule dynamics. We show here that overexpressing ILK in HeLa cells was associated with a shorter duration of mitosis and decreased sensitivity to paclitaxel, a chemotherapeutic agent that suppresses microtubule dynamics. Measurement of interphase microtubule dynamics revealed that ILK overexpression favored microtubule depolymerization, suggesting that microtubule destabilization could be the mechanism behind the decreased sensitivity to paclitaxel, which is known to stabilize microtubules. Conversely, the use of a small molecule inhibitor selective against ILK, QLT-0267, resulted in suppressed microtubule dynamics, demonstrating a new mechanism of action for this compound. We further show that treatment of HeLa cells with QLT-0267 resulted in higher inter-centromere tension in aligned chromosomes during mitosis, slower microtubule regrowth after cold depolymerization and the presence of a more stable population of spindle microtubules. These results demonstrate that ILK regulates microtubule dynamics in both interphase and mitotic cells.

  11. Disrupted in schizophrenia 1 (DISC1) inhibits glioblastoma development by regulating mitochondria dynamics

    Science.gov (United States)

    Hu, Zhifang; Hu, Fengrui; liu, Dou; Gao, Lei; Gou, Xingchun; Jin, Weilin

    2016-01-01

    Glioblastoma(GBM) is one of the most common and aggressive malignant primary tumors of the central nervous system and mitochondria have been proposed to participate in GBM tumorigenesis. Previous studies have identified a potential role of Disrupted in Schizophrenia 1 (DISC1), a multi-compartmentalized protein, in mitochondria. But whether DISC1 could regulate GBM tumorigenesis via mitochondria is still unknown. We determined the expression level of DISC1 by both bioinformatics analysis and tissue analysis, and found that DISC1 was highly expressed in GBM. Knocking down of DISC1 by shRNA in GBM cells significantly inhibited cell proliferation both in vitro and in vivo. In addition, down-regulation of DISC1 decreased cell migration and invasion of GBM and self renewal capacity of glioblastoma stem-like cells. Furthermore, multiple independent rings or spheres could be observed in mitochondria in GBM depleted of DISC1, while normal filamentous morphology was observed in control cells, demonstrating that DISC1 affected the mitochondrial dynamic. Dynamin-related protein 1 (Drp1) was reported to contribute to mitochondrial dynamic regulation and influence glioma cells proliferation and invasion by RHOA/ ROCK1 pathway. Our data showed a significant decrease of Drp1 both in mRNA and protein level in GBM lack of DISC1, indicating that DISC1 maybe affect the mitochondrial dynamic by regulating Drp1. Taken together, our findings reveal that DISC1 affects glioblastoma cell development via mitochondria dynamics partly by down regulation of Drp1. PMID:27852062

  12. Dynamic coordinated control laws in multiple agent models

    International Nuclear Information System (INIS)

    Morgan, David S.; Schwartz, Ira B.

    2005-01-01

    We present an active control scheme of a kinetic model of swarming. It has been shown previously that the global control scheme for the model, presented in [Systems Control Lett. 52 (2004) 25], gives rise to spontaneous collective organization of agents into a unified coherent swarm, via steering controls and utilizing long-range attractive and short-range repulsive interactions. We extend these results by presenting control laws whereby a single swarm is broken into independently functioning subswarm clusters. The transition between one coordinated swarm and multiple clustered subswarms is managed simply with a homotopy parameter. Additionally, we present as an alternate formulation, a local control law for the same model, which implements dynamic barrier avoidance behavior, and in which swarm coherence emerges spontaneously

  13. Dynamical systems modeling of early childhood self-regulation.

    Science.gov (United States)

    Cole, Pamela M; Bendezú, Jason J; Ram, Nilam; Chow, Sy-Miin

    2017-06-01

    Self-regulation can be conceptualized in terms of dynamic tension between highly probable reactions (prepotent responses) and use of strategies that can modulate those reactions (executive processes). This study investigated the value of a dynamical systems approach to the study of early childhood self-regulation. Specifically, ordinary differential equations (ODEs) were used to model the interactive influences of 115 36-month-olds' executive processes (strategy use) and prepotent responses to waiting to open a gift (desire for the gift and frustration about waiting to open it). Using a pair of coupled second-order ODEs in a nonlinear mixed effects framework, the study tested predictions for specific within- and between-child patterns of prepotent response-executive process coupling. Dynamic modeling results articulated the limits of 36-month olds' strategic efforts. They engaged executive processes when their prepotent responding levels were high, which delayed the resurgence of prepotent responses, but ultimately did not damp prepotent responding over the course of the wait. There was, however, preliminary evidence that the effectiveness of 36-month-olds' self-regulation depended upon child characteristics. Externalizing behavior problems were associated with more regulatory interference. Temperamental negative affectivity was marginally associated with more regulatory inefficiency. Compared with conventional methods of studying self-regulation, dynamic modeling yielded complementary and unique findings, suggesting its potential. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  14. Dynamic multiple thresholding breast boundary detection algorithm for mammograms

    International Nuclear Information System (INIS)

    Wu, Yi-Ta; Zhou Chuan; Chan, Heang-Ping; Paramagul, Chintana; Hadjiiski, Lubomir M.; Daly, Caroline Plowden; Douglas, Julie A.; Zhang Yiheng; Sahiner, Berkman; Shi Jiazheng; Wei Jun

    2010-01-01

    Purpose: Automated detection of breast boundary is one of the fundamental steps for computer-aided analysis of mammograms. In this study, the authors developed a new dynamic multiple thresholding based breast boundary (MTBB) detection method for digitized mammograms. Methods: A large data set of 716 screen-film mammograms (442 CC view and 274 MLO view) obtained from consecutive cases of an Institutional Review Board approved project were used. An experienced breast radiologist manually traced the breast boundary on each digitized image using a graphical interface to provide a reference standard. The initial breast boundary (MTBB-Initial) was obtained by dynamically adapting the threshold to the gray level range in local regions of the breast periphery. The initial breast boundary was then refined by using gradient information from horizontal and vertical Sobel filtering to obtain the final breast boundary (MTBB-Final). The accuracy of the breast boundary detection algorithm was evaluated by comparison with the reference standard using three performance metrics: The Hausdorff distance (HDist), the average minimum Euclidean distance (AMinDist), and the area overlap measure (AOM). Results: In comparison with the authors' previously developed gradient-based breast boundary (GBB) algorithm, it was found that 68%, 85%, and 94% of images had HDist errors less than 6 pixels (4.8 mm) for GBB, MTBB-Initial, and MTBB-Final, respectively. 89%, 90%, and 96% of images had AMinDist errors less than 1.5 pixels (1.2 mm) for GBB, MTBB-Initial, and MTBB-Final, respectively. 96%, 98%, and 99% of images had AOM values larger than 0.9 for GBB, MTBB-Initial, and MTBB-Final, respectively. The improvement by the MTBB-Final method was statistically significant for all the evaluation measures by the Wilcoxon signed rank test (p<0.0001). Conclusions: The MTBB approach that combined dynamic multiple thresholding and gradient information provided better performance than the breast boundary

  15. 76 FR 23504 - Defense Federal Acquisition Regulation Supplement; Definition of Multiple-Award Contract (DFARS...

    Science.gov (United States)

    2011-04-27

    ... the definition of ``multiple-award contract'' at DFARS 207.107-2. The revised DFARS language is... Defense Acquisition Regulations System 48 CFR Part 207 RIN 0750-AH12 Defense Federal Acquisition Regulation Supplement; Definition of Multiple-Award Contract (DFARS Case 2011-D016) AGENCY: Defense...

  16. Influence of plant growth regulators on axillary shoot multiplication ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-12-17

    Dec 17, 2008 ... containing 3% (w/v) sucrose, 0.8% (w/v) agar, and different concentrations and combinations of plant growth regulators. .... Other plant growth regulators were added to basal medium prior to pH adjustment and sterilization. All cultures were maintained at 25 ± 2°C under a 16 h .... In contrast, when the.

  17. Self-regulated dynamical criticality in human ECoG

    Directory of Open Access Journals (Sweden)

    Guillermo eSolovey

    2012-07-01

    Full Text Available Mounting experimental and theoretical results indicate that neural systems are poised near a critical state. In human subjects, however, most evidence comes from functional MRI studies, an indirect measurement of neuronal activity with poor temporal resolution. Electrocorticography (ECoG provides a unique window into human brain activity: each electrode records, with high temporal resolution, the activity resulting from the sum of the local field potentials of sim 10^5 neurons. We show that the human brain ECoG recordings display features of self-regulated dynamical criticality: dynamical modes of activation drift around the critical stability threshold, moving in and out of the unstable region and equilibrating the global dynamical state at a very fast time scale. Moreover, the analysis also reveals differences between the resting state and a motor task, associated with increased stability of a fraction of the dynamical modes.

  18. Dynamic collimator trajectory algorithm for multiple metastases dynamic conformal arc treatment planning.

    Science.gov (United States)

    MacDonald, R Lee; Thomas, Christopher G; Syme, Alasdair

    2018-01-01

    To develop an algorithm for dynamic collimator positioning to optimize beam's eye view (BEV) fitting of targets in dynamic conformal arc (DCA)-based radiotherapy procedures, of particular use in multiple metastases stereotactic radiosurgery procedures. A trajectory algorithm was developed to dynamically modify the angle of the collimator as a function of arc-based control point to provide optimized collimation of target volume(s). Central to this algorithm is a concept denoted herein as "whitespace" defined as any nontarget area in the BEV that is not covered by any collimation system and is open to exposure from the radiation beam. Calculating whitespace at all collimator angles and every control point, a two-dimensional topographical map depicting the tightness-of-fit of the MLC was generated. A bidirectional gradient trajectory algorithm identified a number of candidate trajectories of continuous collimator motion. Minimization of integrated whitespace was used to identify an optimal solution for the navigation of the parameter space. Plans with dynamic collimator trajectories were designed for multiple metastases targets and were compared with fixed collimator angle dynamic conformal arc (DCA) plans and standard VMAT plans. Algorithm validation was performed on simple test cases with known solutions. The whitespace metric showed a strong correlation (R 2 = 0.90) with mean dose to proximal normal tissue. Seventeen cases were studied using our algorithm to generate dynamic conformal arc (DCA) plans with optimized collimator trajectories for three and four target SRS patients and comparing them to DCA plans generated with optimized fixed collimator angles per arc and standard VMAT plans generated via template. Optimized collimator trajectories were found to produce a reduction in monitor units of up to 49.7 ± 5.1% when compared to VMAT across 17 patients, and all organ-at-risk and normal brain metrics were found to be superior or comparable. Dynamic collimator

  19. Stakeholder cooperation: regulating a uranium mine with multiple statutory approvals

    International Nuclear Information System (INIS)

    Bush, M.

    2010-01-01

    Ranger Uranium Mine operates under an Authorisation issued by the Northern Territory Government. In addition, the site is regulated by a set of Environmental Requirements attached to the uranium export permit issued by the Australian Government Department of Resources, Energy and Tourism. A Heap Leach facility proposed for the site could result in a third approval being issued, in accordance with the Environmental Protection and Biodiversity Conservation Act 1999 (EPBC Act). Finding the correct balance to regulate the mine in light of these approvals will be a challenge for the range of stakeholders involved in regulation and oversight of this operation. (author)

  20. Stakeholder cooperation: regulating a uranium mine with multiple statutory approvals

    Energy Technology Data Exchange (ETDEWEB)

    Bush, M., E-mail: Michelle.Bush@environment.gov.au [Dept. of the Environment, Water, Heritage and the Arts, Supervising Scientist Division, Darwin, NT (Australia)

    2010-07-01

    Ranger Uranium Mine operates under an Authorisation issued by the Northern Territory Government. In addition, the site is regulated by a set of Environmental Requirements attached to the uranium export permit issued by the Australian Government Department of Resources, Energy and Tourism. A Heap Leach facility proposed for the site could result in a third approval being issued, in accordance with the Environmental Protection and Biodiversity Conservation Act 1999 (EPBC Act). Finding the correct balance to regulate the mine in light of these approvals will be a challenge for the range of stakeholders involved in regulation and oversight of this operation. (author)

  1. Generative modelling of regulated dynamical behavior in cultured neuronal networks

    Science.gov (United States)

    Volman, Vladislav; Baruchi, Itay; Persi, Erez; Ben-Jacob, Eshel

    2004-04-01

    The spontaneous activity of cultured in vitro neuronal networks exhibits rich dynamical behavior. Despite the artificial manner of their construction, the networks’ activity includes features which seemingly reflect the action of underlying regulating mechanism rather than arbitrary causes and effects. Here, we study the cultured networks dynamical behavior utilizing a generative modelling approach. The idea is to include the minimal required generic mechanisms to capture the non-autonomous features of the behavior, which can be reproduced by computer modelling, and then, to identify the additional features of biotic regulation in the observed behavior which are beyond the scope of the model. Our model neurons are composed of soma described by the two Morris-Lecar dynamical variables (voltage and fraction of open potassium channels), with dynamical synapses described by the Tsodyks-Markram three variables dynamics. The model neuron satisfies our self-consistency test: when fed with data recorded from a real cultured networks, it exhibits dynamical behavior very close to that of the networks’ “representative” neuron. Specifically, it shows similar statistical scaling properties (approximated by similar symmetric Lévy distribution with finite mean). A network of such M-L elements spontaneously generates (when weak “structured noise” is added) synchronized bursting events (SBEs) similar to the observed ones. Both the neuronal statistical scaling properties within the bursts and the properties of the SBEs time series show generative (a new discussed concept) agreement with the recorded data. Yet, the model network exhibits different structure of temporal variations and does not recover the observed hierarchical temporal ordering, unless fed with recorded special neurons (with much higher rates of activity), thus indicating the existence of self-regulation mechanisms. It also implies that the spontaneous activity is not simply noise-induced. Instead, the

  2. Dynamics and heterogeneity of brain damage in multiple sclerosis

    KAUST Repository

    Kotelnikova, Ekaterina

    2017-10-26

    Multiple Sclerosis (MS) is an autoimmune disease driving inflammatory and degenerative processes that damage the central nervous system (CNS). However, it is not well understood how these events interact and evolve to evoke such a highly dynamic and heterogeneous disease. We established a hypothesis whereby the variability in the course of MS is driven by the very same pathogenic mechanisms responsible for the disease, the autoimmune attack on the CNS that leads to chronic inflammation, neuroaxonal degeneration and remyelination. We propose that each of these processes acts more or less severely and at different times in each of the clinical subgroups. To test this hypothesis, we developed a mathematical model that was constrained by experimental data (the expanded disability status scale [EDSS] time series) obtained from a retrospective longitudinal cohort of 66 MS patients with a long-term follow-up (up to 20 years). Moreover, we validated this model in a second prospective cohort of 120 MS patients with a three-year follow-up, for which EDSS data and brain volume time series were available. The clinical heterogeneity in the datasets was reduced by grouping the EDSS time series using an unsupervised clustering analysis. We found that by adjusting certain parameters, albeit within their biological range, the mathematical model reproduced the different disease courses, supporting the dynamic CNS damage hypothesis to explain MS heterogeneity. Our analysis suggests that the irreversible axon degeneration produced in the early stages of progressive MS is mainly due to the higher rate of myelinated axon degeneration, coupled to the lower capacity for remyelination. However, and in agreement with recent pathological studies, degeneration of chronically demyelinated axons is not a key feature that distinguishes this phenotype. Moreover, the model reveals that lower rates of axon degeneration and more rapid remyelination make relapsing MS more resilient than the

  3. Regulation of mitochondrial dynamics in astrocytes: Mechanisms, consequences, and unknowns.

    Science.gov (United States)

    Jackson, Joshua G; Robinson, Michael B

    2017-11-03

    Astrocytes are the major glial cell in the central nervous system. These polarized cells possess numerous processes that ensheath the vasculature and contact synapses. Astrocytes play important roles in synaptic signaling, neurotransmitter synthesis and recycling, control of nutrient uptake, and control of local blood flow. Many of these processes depend on local metabolism and/or energy utilization. While astrocytes respond to increases in neuronal activity and metabolic demand by upregulating glycolysis and glycogenolysis, astrocytes also possess significant capacity for oxidative (mitochondrial) metabolism. Mitochondria mediate energy supply and metabolism, cellular survival, ionic homeostasis, and proliferation. These organelles are dynamic structures undergoing extensive fission and fusion, directed movement along cytoskeletal tracts, and degradation. While many of the mechanisms underlying the dynamics of these organelles and their physiologic roles have been characterized in neurons and other cells, the roles that mitochondrial dynamics play in glial physiology is less well understood. Recent work from several laboratories has demonstrated that mitochondria are present within the fine processes of astrocytes, that their movement is regulated, and that they contribute to local Ca 2+ signaling within the astrocyte. They likely play a role in local ATP production and metabolism, particularly that of glutamate. Here we will review these and other findings describing the mechanism by which mitochondrial dynamics are regulated in astrocytes, how mitochondrial dynamics might influence astrocyte and brain metabolism, and draw parallels to mitochondrial dynamics in neurons. Additionally, we present new analyses of the size, distribution, and dynamics of mitochondria in astrocytes performed using in vivo using 2-photon microscopy. © 2017 Wiley Periodicals, Inc.

  4. miR-181a regulates multiple pathways in hypopharyngeal ...

    African Journals Online (AJOL)

    Expression of four pathway reporters were significantly increased (p53/DNA damage, TGFβ, MAPK/ERK and MAPK/JNK), while expression of two pathway reporters were decreased (Wnt and NFkB) upon miR-181a down-regulation. Notch, Myc/Max, hypoxia and cell cycle/pRB-E2F pathways were not significantly affected ...

  5. Supporting Affect Regulation in Children With Multiple Disabilities During Psychotherapy: A Multiple Case Design Study of Therapeutic Attachment. [Miscellaneous Article

    NARCIS (Netherlands)

    Schuengel, C; Sterkenburg, P S; Jeczynski, P; Janssen, C G C; Jongbloed, G

    2009-01-01

    : In a controlled multiple case design study, the development of a therapeutic relationship and its role in affect regulation were studied in 6 children with visual disabilities, severe intellectual disabilities, severe challenging behavior, and prolonged social deprivation. In the 1st phase,

  6. Modeling the effector - regulatory T cell cross-regulation reveals the intrinsic character of relapses in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Torrealdea Javier

    2011-07-01

    Full Text Available Abstract Background The relapsing-remitting dynamics is a hallmark of autoimmune diseases such as Multiple Sclerosis (MS. Although current understanding of both cellular and molecular mechanisms involved in the pathogenesis of autoimmune diseases is significant, how their activity generates this prototypical dynamics is not understood yet. In order to gain insight about the mechanisms that drive these relapsing-remitting dynamics, we developed a computational model using such biological knowledge. We hypothesized that the relapsing dynamics in autoimmunity can arise through the failure in the mechanisms controlling cross-regulation between regulatory and effector T cells with the interplay of stochastic events (e.g. failure in central tolerance, activation by pathogens that are able to trigger the immune system. Results The model represents five concepts: central tolerance (T-cell generation by the thymus, T-cell activation, T-cell memory, cross-regulation (negative feedback between regulatory and effector T-cells and tissue damage. We enriched the model with reversible and irreversible tissue damage, which aims to provide a comprehensible link between autoimmune activity and clinical relapses and active lesions in the magnetic resonances studies in patients with Multiple Sclerosis. Our analysis shows that the weakness in this negative feedback between effector and regulatory T-cells, allows the immune system to generate the characteristic relapsing-remitting dynamics of autoimmune diseases, without the need of additional environmental triggers. The simulations show that the timing at which relapses appear is highly unpredictable. We also introduced targeted perturbations into the model that mimicked immunotherapies that modulate effector and regulatory populations. The effects of such therapies happened to be highly dependent on the timing and/or dose, and on the underlying dynamic of the immune system. Conclusion The relapsing dynamic in MS

  7. Dynamic berth and quay crane allocation for multiple berth positions and quay cranes

    NARCIS (Netherlands)

    Tri Cahyono, Rully; Flonk, E.J.; Jayawardhana, Bayu

    2015-01-01

    We study in this paper a dynamic berth and quay cranes allocation strategy in general seaport container terminals. We develop a dynamical model that describes the operation of berthing process with multiple discrete berthing positions and multiple quay cranes. Based on the proposed model, we develop

  8. Mouse ribosomal RNA genes contain multiple differentially regulated variants.

    Directory of Open Access Journals (Sweden)

    Hung Tseng

    2008-03-01

    Full Text Available Previous cytogenetic studies suggest that various rDNA chromosomal loci are not equally active in different cell types. Consistent with this variability, rDNA polymorphism is well documented in human and mouse. However, attempts to identify molecularly rDNA variant types, which are regulated individually (i.e., independent of other rDNA variants and tissue-specifically, have not been successful. We report here the molecular cloning and characterization of seven mouse rDNA variants (v-rDNA. The identification of these v-rDNAs was based on restriction fragment length polymorphisms (RFLPs, which are conserved among individuals and mouse strains. The total copy number of the identified variants is less than 100 and the copy number of each individual variant ranges from 4 to 15. Sequence analysis of the cloned v-rDNA identified variant-specific single nucleotide polymorphisms (SNPs in the transcribed region. These SNPs were used to develop a set of variant-specific PCR assays, which permitted analysis of the v-rDNAs' expression profiles in various tissues. These profiles show that three v-rDNAs are expressed in all tissues (constitutively active, two are expressed in some tissues (selectively active, and two are not expressed (silent. These expression profiles were observed in six individuals from three mouse strains, suggesting the pattern is not randomly determined. Thus, the mouse rDNA array likely consists of genetically distinct variants, and some are regulated tissue-specifically. Our results provide the first molecular evidence for cell-type-specific regulation of a subset of rDNA.

  9. Endothelin-1 Regulation of Exercise-Induced Changes in Flow: Dynamic Regulation of Vascular Tone

    Directory of Open Access Journals (Sweden)

    Robert M. Rapoport

    2017-10-01

    Full Text Available Although endothelin (ET-1 is a highly potent vasoconstrictor with considerable efficacy in numerous vascular beds, the role of endogenous ET-1 in the regulation of vascular tone remains unclear. The perspective that ET-1 plays little role in the on-going regulation of vascular tone at least under physiologic conditions is supported by findings that potential ET-1 constriction is minimized by the release of the vasodilator and ET-1 synthesis inhibitor, nitric oxide (NO. Indeed, ET-1 release and constriction is self-limited by ET-1-induced, endothelial ETB receptor-mediated release of NO. Moreover, even if the balance between ET-1 and NO were reversed as the result of lowered NO activity, as occurs in a number of pathophysiologies associated with endothelial dysfunction, the well-known resistance of ET-1 constriction to reversal (as determined with exogenous ET-1 precludes ET-1 in the dynamic, i.e., moment-to-moment, regulation of vascular tone. On the other hand, and as presently reviewed, findings of ET-1-dependent modulation of organ blood flow with exercise under physiologic conditions demonstrate the dynamic regulation of vascular tone by ET-1. We speculate that this regulation is mediated at least in part through changes in ET-1 synthesis/release caused by pulsatile flow-induced shear stress and NO.

  10. Relaxation dynamics in the presence of pulse multiplicative noise sources with different correlation properties

    Science.gov (United States)

    Kargovsky, A. V.; Chichigina, O. A.; Anashkina, E. I.; Valenti, D.; Spagnolo, B.

    2015-10-01

    The relaxation dynamics of a system described by a Langevin equation with pulse multiplicative noise sources with different correlation properties is considered. The solution of the corresponding Fokker-Planck equation is derived for Gaussian white noise. Moreover, two pulse processes with regulated periodicity are considered as a noise source: the dead-time-distorted Poisson process and the process with fixed time intervals, which is characterized by an infinite correlation time. We find that the steady state of the system is dependent on the correlation properties of the pulse noise. An increase of the noise correlation causes the decrease of the mean value of the solution at the steady state. The analytical results are in good agreement with the numerical ones.

  11. Dynamic regulation of neurotransmitter specification: Relevance to nervous system homeostasis

    Science.gov (United States)

    Borodinsky, Laura N.; Belgacem, Yesser Hadj; Swapna, Immani; Sequerra, Eduardo Bouth

    2013-01-01

    During nervous system development the neurotransmitter identity changes and coexpression of several neurotransmitters is a rather generalized feature of developing neurons. In the mature nervous system, different physiological and pathological circumstances recreate this phenomenon. The rules of neurotransmitter respecification are multiple. Among them, the goal of assuring balanced excitability appears as an important driving force for the modifications in neurotransmitter phenotype expression. The functional consequences of these dynamic revisions in neurotransmitter identity span a varied range, from fine-tuning the developing neural circuit to modifications in addictive and locomotor behaviors. Current challenges include determining the mechanisms underlying neurotransmitter phenotype respecification and how they intersect with genetic programs of neuronal specialization. PMID:23270605

  12. Multiple equilibria and limit cycles in evolutonary games with Logit Dynamics

    NARCIS (Netherlands)

    Hommes, C.H.; Ochea, M.I.

    2012-01-01

    This note shows, by means of two simple, three-strategy games, the existence of stable periodic orbits and of multiple, interior steady states in a smooth version of the Best-Response Dynamics, the Logit Dynamics. The main finding is that, unlike Replicator Dynamics, generic Hopf bifurcation and

  13. Environmental regulation and the export dynamics of energy technologies

    International Nuclear Information System (INIS)

    Costantini, Valeria; Crespi, Francesco

    2008-01-01

    The pollution haven hypothesis affirms that an open market regime will encourage the flow of low-technology polluting industries towards developing countries because of potential comparative advantages related to low environmental standards. In contrast, the hypothesis suggested by Porter and van der Linde claims that innovating firms operate in a dynamic competitive situation which allows global diffusion of environmental-friendly technologies. Environmental regulation may represent a relevant mechanism through which technological change is induced. In this way, countries that are subject to more stringent environmental regulations may become net exporters of environmental technologies. This paper provides new evidence on the evolution of export flows of environmental technologies across different countries for the energy sector. Advanced economies, particularly the European Union, have increasingly focused on the role of energy policies as tools for sustaining the development path. The Kyoto Protocol commitments, together with growing import dependence on energy products, have brought attention to the analysis of innovation processes in this specific sector. The analysis uses a gravity model in order to test the determinants and the transmission channels through which environmental technologies for renewable energies and energy efficiency are exported to advanced and developing countries. Our results are consistent with the Porter and van der Linde hypothesis where environmental regulation represents a significant source of comparative advantages. What strongly emerges is that the stringency of environmental regulation supplemented by the strength of the National Innovation System is a crucial driver of export performance in the field of energy technologies. (author)

  14. Dynamic regulation of hepatic lipid droplet properties by diet.

    Science.gov (United States)

    Crunk, Amanda E; Monks, Jenifer; Murakami, Aya; Jackman, Matthew; Maclean, Paul S; Ladinsky, Mark; Bales, Elise S; Cain, Shannon; Orlicky, David J; McManaman, James L

    2013-01-01

    Cytoplasmic lipid droplets (CLD) are organelle-like structures that function in neutral lipid storage, transport and metabolism through the actions of specific surface-associated proteins. Although diet and metabolism influence hepatic CLD levels, how they affect CLD protein composition is largely unknown. We used non-biased, shotgun, proteomics in combination with metabolic analysis, quantitative immunoblotting, electron microscopy and confocal imaging to define the effects of low- and high-fat diets on CLD properties in fasted-refed mice. We found that the hepatic CLD proteome is distinct from that of CLD from other mammalian tissues, containing enzymes from multiple metabolic pathways. The hepatic CLD proteome is also differentially affected by dietary fat content and hepatic metabolic status. High fat feeding markedly increased the CLD surface density of perilipin-2, a critical regulator of hepatic neutral lipid storage, whereas it reduced CLD levels of betaine-homocysteine S-methyltransferase, an enzyme regulator of homocysteine levels linked to fatty liver disease and hepatocellular carcinoma. Collectively our data demonstrate that the hepatic CLD proteome is enriched in metabolic enzymes, and that it is qualitatively and quantitatively regulated by diet and metabolism. These findings implicate CLD in the regulation of hepatic metabolic processes, and suggest that their properties undergo reorganization in response to hepatic metabolic demands.

  15. Synthetic RORγ agonists regulate multiple pathways to enhance antitumor immunity

    Science.gov (United States)

    Hu, Xiao; Liu, Xikui; Moisan, Jacques; Wang, Yahong; Lesch, Charles A.; Spooner, Chauncey; Morgan, Rodney W.; Zawidzka, Elizabeth M.; Mertz, David; Bousley, Dick; Majchrzak, Kinga; Kryczek, Ilona; Taylor, Clarke; Van Huis, Chad; Skalitzky, Don; Hurd, Alexander; Aicher, Thomas D.; Toogood, Peter L.; Glick, Gary D.; Paulos, Chrystal M.; Zou, Weiping; Carter, Laura L.

    2016-01-01

    ABSTRACT RORγt is the key transcription factor controlling the development and function of CD4+ Th17 and CD8+ Tc17 cells. Across a range of human tumors, about 15% of the CD4+ T cell fraction in tumor-infiltrating lymphocytes are RORγ+ cells. To evaluate the role of RORγ in antitumor immunity, we have identified synthetic, small molecule agonists that selectively activate RORγ to a greater extent than the endogenous agonist desmosterol. These RORγ agonists enhance effector function of Type 17 cells by increasing the production of cytokines/chemokines such as IL-17A and GM-CSF, augmenting expression of co-stimulatory receptors like CD137, CD226, and improving survival and cytotoxic activity. RORγ agonists also attenuate immunosuppressive mechanisms by curtailing Treg formation, diminishing CD39 and CD73 expression, and decreasing levels of co-inhibitory receptors including PD-1 and TIGIT on tumor-reactive lymphocytes. The effects of RORγ agonists were not observed in RORγ−/− T cells, underscoring the selective on-target activity of the compounds. In vitro treatment of tumor-specific T cells with RORγ agonists, followed by adoptive transfer to tumor-bearing mice is highly effective at controlling tumor growth while improving T cell survival and maintaining enhanced IL-17A and reduced PD-1 in vivo. The in vitro effects of RORγ agonists translate into single agent, immune system-dependent, antitumor efficacy when compounds are administered orally in syngeneic tumor models. RORγ agonists integrate multiple antitumor mechanisms into a single therapeutic that both increases immune activation and decreases immune suppression resulting in robust inhibition of tumor growth. Thus, RORγ agonists represent a novel immunotherapy approach for cancer. PMID:28123897

  16. Fast Responding Voltage Regulator and Dynamic VAR Compensator

    Energy Technology Data Exchange (ETDEWEB)

    Divan, Deepak [Varentec, Incorporated, San Jose, CA (United States); Moghe, Rohit [Varentec, Incorporated, San Jose, CA (United States); Tholomier, Damien [Varentec, Incorporated, San Jose, CA (United States)

    2014-12-31

    The objectives of this project were to develop a dynamic VAR compensator (DVC) for voltage regulation through VAR support to demonstrate the ability to achieve greater levels of voltage control on electricity distribution networks, and faster response compared to existing grid technology. The goal of the project was to develop a prototype Fast Dynamic VAR Compensator (Fast DVC) hardware device, and this was achieved. In addition to developing the dynamic VAR compensator device, Varentec in partnership with researchers at North Carolina State University (NCSU) successfully met the objectives to model the potential positive impact of such DVCs on representative power networks. This modeling activity validated the ability of distributed dynamic VAR compensators to provide fast voltage regulation and reactive power control required to respond to grid disturbances under high penetration of fluctuating and intermittent distributed energy resources (DERs) through extensive simulation studies. Specifically the following tasks were set to be accomplished: 1) Development of dynamic VAR compensator to support dynamic voltage variations on the grid through VAR control 2) Extensive testing of the DVC in the lab environment 3) Present the operational DVC device to the DOE at Varentec’s lab 4) Formulation of a detailed specification sheet, unit assembly document, test setup document, unit bring-up plan, and test plan 5) Extensive simulations of the DVC in a system with high PV penetration. Understanding the operation with many DVC on a single distribution system 6) Creation and submittal of quarterly and final reports conveying the design documents, unit performance data, modeling simulation charts and diagrams, and summary explanations of the satisfaction of program goals. This report details the various efforts that led to the development of the Fast DVC as well as the modeling & simulation results. The report begins with the introduction in Section II which outlines the

  17. EEN regulates the proliferation and survival of multiple myeloma cells by potentiating IGF-1 secretion

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Er-Wen [Guangzhou Institute of Forensic Science, Guangzhou (China); Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou (China); Xue, Sheng-Jiang [Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou (China); Li, Xiao-Yan [Department of Pharmacy, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou (China); Xu, Suo-Wen [Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou (China); Cheng, Jian-Ding; Zheng, Jin-Xiang [Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou (China); Shi, He; Lv, Guo-Li; Li, Zhi-Gang; Li, Yue; Liu, Chang-Hui; Chen, Xiao-Hui; Liu, Hong [Guangzhou Institute of Forensic Science, Guangzhou (China); Li, Jie, E-mail: mdlijie@sina.com [Department of Anaesthesiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou (China); Liu, Chao, E-mail: liuchaogaj@21cn.com [Guangzhou Institute of Forensic Science, Guangzhou (China)

    2014-05-02

    Highlights: • Levels of EEN expression paralleled with the rate of cell proliferation. • EEN was involved in the proliferation and survival of multiple myeloma (MM) cells. • EEN regulated the activity of IGF-1-Akt/mTOR pathway. • EEN regulated proliferation and survival of MM cells by enhancing IGF-1 secretion. - Abstract: The molecular mechanisms of multiple myeloma are not well defined. EEN is an endocytosis-regulating molecule. Here we report that EEN regulates the proliferation and survival of multiple myeloma cells, by regulating IGF-1 secretion. In the present study, we observed that EEN expression paralleled with cell proliferation, EEN accelerated cell proliferation, facilitated cell cycle transition from G1 to S phase by regulating cyclin-dependent kinases (CDKs) pathway, and delayed cell apoptosis via Bcl2/Bax-mitochondrial pathway. Mechanistically, we found that EEN was indispensable for insulin-like growth factor-1 (IGF-1) secretion and the activation of protein kinase B-mammalian target of rapamycin (Akt-mTOR) pathway. Exogenous IGF-1 overcame the phenotype of EEN depletion, while IGF-1 neutralization overcame that of EEN over-expression. Collectively, these data suggest that EEN may play a pivotal role in excessive cell proliferation and insufficient cell apoptosis of bone marrow plasma cells in multiple myeloma. Therefore, EEN may represent a potential diagnostic marker or therapeutic target for multiple myeloma.

  18. EEN regulates the proliferation and survival of multiple myeloma cells by potentiating IGF-1 secretion

    International Nuclear Information System (INIS)

    Huang, Er-Wen; Xue, Sheng-Jiang; Li, Xiao-Yan; Xu, Suo-Wen; Cheng, Jian-Ding; Zheng, Jin-Xiang; Shi, He; Lv, Guo-Li; Li, Zhi-Gang; Li, Yue; Liu, Chang-Hui; Chen, Xiao-Hui; Liu, Hong; Li, Jie; Liu, Chao

    2014-01-01

    Highlights: • Levels of EEN expression paralleled with the rate of cell proliferation. • EEN was involved in the proliferation and survival of multiple myeloma (MM) cells. • EEN regulated the activity of IGF-1-Akt/mTOR pathway. • EEN regulated proliferation and survival of MM cells by enhancing IGF-1 secretion. - Abstract: The molecular mechanisms of multiple myeloma are not well defined. EEN is an endocytosis-regulating molecule. Here we report that EEN regulates the proliferation and survival of multiple myeloma cells, by regulating IGF-1 secretion. In the present study, we observed that EEN expression paralleled with cell proliferation, EEN accelerated cell proliferation, facilitated cell cycle transition from G1 to S phase by regulating cyclin-dependent kinases (CDKs) pathway, and delayed cell apoptosis via Bcl2/Bax-mitochondrial pathway. Mechanistically, we found that EEN was indispensable for insulin-like growth factor-1 (IGF-1) secretion and the activation of protein kinase B-mammalian target of rapamycin (Akt-mTOR) pathway. Exogenous IGF-1 overcame the phenotype of EEN depletion, while IGF-1 neutralization overcame that of EEN over-expression. Collectively, these data suggest that EEN may play a pivotal role in excessive cell proliferation and insufficient cell apoptosis of bone marrow plasma cells in multiple myeloma. Therefore, EEN may represent a potential diagnostic marker or therapeutic target for multiple myeloma

  19. Reconstructing nonlinear dynamic models of gene regulation using stochastic sampling

    Directory of Open Access Journals (Sweden)

    Reinelt Gerhard

    2009-12-01

    Full Text Available Abstract Background The reconstruction of gene regulatory networks from time series gene expression data is one of the most difficult problems in systems biology. This is due to several reasons, among them the combinatorial explosion of possible network topologies, limited information content of the experimental data with high levels of noise, and the complexity of gene regulation at the transcriptional, translational and post-translational levels. At the same time, quantitative, dynamic models, ideally with probability distributions over model topologies and parameters, are highly desirable. Results We present a novel approach to infer such models from data, based on nonlinear differential equations, which we embed into a stochastic Bayesian framework. We thus address both the stochasticity of experimental data and the need for quantitative dynamic models. Furthermore, the Bayesian framework allows it to easily integrate prior knowledge into the inference process. Using stochastic sampling from the Bayes' posterior distribution, our approach can infer different likely network topologies and model parameters along with their respective probabilities from given data. We evaluate our approach on simulated data and the challenge #3 data from the DREAM 2 initiative. On the simulated data, we study effects of different levels of noise and dataset sizes. Results on real data show that the dynamics and main regulatory interactions are correctly reconstructed. Conclusions Our approach combines dynamic modeling using differential equations with a stochastic learning framework, thus bridging the gap between biophysical modeling and stochastic inference approaches. Results show that the method can reap the advantages of both worlds, and allows the reconstruction of biophysically accurate dynamic models from noisy data. In addition, the stochastic learning framework used permits the computation of probability distributions over models and model parameters

  20. CGGBP1-CTCF dynamics in regulation of chromosomal interactions

    Directory of Open Access Journals (Sweden)

    Divyesh Patel

    2017-10-01

    Full Text Available Genome organisation and gene expression is regulated by specific DNA sequences that include “insulator elements”. Insulator proteins, such as CTCF bind to insulator elements to block spreading of silent chromatin in-cis or inhibit interactions between transcriptional enhancers and promoters. By binding to insulators in a methylation-sensittive manner, CTCF establishes and maintains contrasting transcription patterns on either side of the insulator elements [1]. Though details of CTCF-insulator activities have been worked out, mechanisms of regulation of insulator activity by other proteins is unknown. CTCF-binding insulators are retrotransposon-derived, the same elements to which CGGBP1 binds making CGGBP1 a candidate insulator regulator factor [2]. Objective is to explore role of CGGBP1-CTCF dynamics in regulation of insulator activity. 1064Sk skin fibroblasts were grown in presence or absence of CGGBP1 in growth stimulated or starved condition. ChIP-seq was performed to identify CGGBP1-binding DNA sequence motifs [3]. We have observed a strong overlap between binding sites of CTCF and CGGBP1 [4, 5].  CGGBP1 and CTCF seem to share the retrotransposons-derived M1 and M2 motifs. Unlike in quiescent cells, growth factor-stimulation increased CGGBP1 binding to CTCF-CGGBP1 binding sites with decreased CTCF insulator activity. The distance between CGGBP1 M1 and M2 motifs was longer in quiescent cells as compared to growth stimulated cells. Our results suggest that CGGBP1 negatively regulates CTCF insulator activity in normal cells in a growth signal-dependent manner.

  1. Precise regulation of gene expression dynamics favors complex promoter architectures.

    Directory of Open Access Journals (Sweden)

    Dirk Müller

    2009-01-01

    Full Text Available Promoters process signals through recruitment of transcription factors and RNA polymerase, and dynamic changes in promoter activity constitute a major noise source in gene expression. However, it is barely understood how complex promoter architectures determine key features of promoter dynamics. Here, we employ prototypical promoters of yeast ribosomal protein genes as well as simplified versions thereof to analyze the relations among promoter design, complexity, and function. These promoters combine the action of a general regulatory factor with that of specific transcription factors, a common motif of many eukaryotic promoters. By comprehensively analyzing stationary and dynamic promoter properties, this model-based approach enables us to pinpoint the structural characteristics underlying the observed behavior. Functional tradeoffs impose constraints on the promoter architecture of ribosomal protein genes. We find that a stable scaffold in the natural design results in low transcriptional noise and strong co-regulation of target genes in the presence of gene silencing. This configuration also exhibits superior shut-off properties, and it can serve as a tunable switch in living cells. Model validation with independent experimental data suggests that the models are sufficiently realistic. When combined, our results offer a mechanistic explanation for why specific factors are associated with low protein noise in vivo. Many of these findings hold for a broad range of model parameters and likely apply to other eukaryotic promoters of similar structure.

  2. EWSR1 regulates mitosis by dynamically influencing microtubule acetylation.

    Science.gov (United States)

    Wang, Yi-Long; Chen, Hui; Zhan, Yi-Qun; Yin, Rong-Hua; Li, Chang-Yan; Ge, Chang-Hui; Yu, Miao; Yang, Xiao-Ming

    2016-08-17

    EWSR1, participating in transcription and splicing, has been identified as a translocation partner for various transcription factors, resulting in translocation, which in turn plays crucial roles in tumorigenesis. Recent studies have investigated the role of EWSR1 in mitosis. However, the effect of EWSR1 on mitosis is poorly understood. Here, we observed that depletion of EWSR1 resulted in cell cycle arrest in the mitotic phase, mainly due to an increase in the time from nuclear envelope breakdown to metaphase, resulting in a high percentage of unaligned chromosomes and multipolar spindles. We also demonstrated that EWSR1 is a spindle-associated protein that interacts with α-tubulin during mitosis. EWSR1 depletion increased the cold-sensitivity of spindle microtubules, and decreased the rate of spindle assembly. EWSR1 regulated the level of microtubule acetylation in the mitotic spindle; microtubule acetylation was rescued in EWSR1-depleted mitotic cells following suppression of HDAC6 activity by its specific inhibitor or siRNA treatment. In summary, these results suggest that EWSR1 regulates the acetylation of microtubules in a cell cycle-dependent manner through its dynamic location on spindle MTs, and may be a novel regulator for mitosis progress independent of its translocation.

  3. Dynamic protein complexes regulate NF-kappaB signaling.

    Science.gov (United States)

    Wegener, E; Krappmann, D

    2008-01-01

    NF-kappaB is a major regulator of the first-line defense against invading pathogens, antigen-specific adaptive immune responses or chemical stress. Stimulation either by extracellular ligands (e.g., inflammatory cytokines, microbial pathogens, peptide antigens) or by intracellular Stressors (e.g., genotoxic drugs) initiates signal-specific pathways that all converge at the IkappaB kinase (IKK) complex, the gatekeeper for NF-kappaB activation. During recent years, considerable progress has been made in understanding the function of NF-kappaB in the regulation of cell growth, survival and apoptosis. In this review, we will focus on the regulation of large signaling complexes on the route to NF-kappaB. Recently published data demonstrate that the assembly, maintenance and activity of the IKK complex determine downstream activation of NF-kappaB. In addition, dynamic complexes upstream of IKK are formed in response to tumor necrosis factor (TNF), antigenic peptides or DNA-damaging agents. Clustering of signaling adaptors promotes the association and activation of ubiquitin ligases that trigger the conjugation of regulatory ubiquitin to target proteins. Ubiquitination serves as a platform to recruit the IKK complex and potentially other protein kinases to trigger IKK activation. These findings support a concept whereby protein complex assembly induces regulatory ubiquitination, which in turn recruits and activates protein kinases. Notably, the great interest in a detailed description of the mechanisms that regulate NF-kappaB activity stems from many observations that link dysregulated NF-kappaB signaling with the onset or progression of various diseases, including cancer, chronic inflammation, cardiovascular disorders and neurodegenerative diseases. Thus, the formation of large signaling clusters and regulatory ubiquitin chains represents promising targets for pharmacological intervention to modulate NF-kappaB signal transduction in disease.

  4. Multiple time scale dynamics in the breakdown of superhydrophobicity

    NARCIS (Netherlands)

    Pirat, C.; Sbragaglia, M.; Peters, A.M.; Borkent, B.M.; Lammertink, Rob G.H.; Wessling, Matthias; Lohse, Detlef

    2008-01-01

    Drops deposited on rough and hydrophobic surfaces can stay suspended with gas pockets underneath the liquid, then showing very low hydrodynamic resistance. When this superhydrophobic state breaks down, the subsequent wetting process can show different dynamical properties. A suitable choice of the

  5. Sequencing dynamic storage systems with multiple lifts and shuttles

    NARCIS (Netherlands)

    Carlo, Hector J.; Vis, Iris F. A.

    2012-01-01

    New types of Automated Storage and Retrieval Systems (AS/RS) able to achieve high throughput are continuously being developed and require new control polices to take full advantage of the developed system. In this paper, a dynamic storage system has been studied as developed by Vanderlande

  6. Dynamically reconfigurable multiple beam illumination based on optical correlation

    DEFF Research Database (Denmark)

    Glückstad, Jesper; Palima, Darwin; Dam, Jeppe Seidelin

    2009-01-01

    We adapt concepts from optical correlation and optical pattern recognition to propose a method for generating reconfigurable multiple spots with high efficiency. The generated spots correspond to the correlation spikes in optical pattern recognition. In pattern recognition, optimizing...... reconfigurable optical patterns with high efficiency for optical micromanipulation and other applications....

  7. Collision avoidance for multiple Lagrangian dynamical systems with gyroscopic forces

    Directory of Open Access Journals (Sweden)

    Lorenzo Sabattini

    2017-01-01

    Full Text Available This article introduces a novel methodology for dealing with collision avoidance for groups of mobile robots. In particular, full dynamics are considered, since each robot is modeled as a Lagrangian dynamical system moving in a three-dimensional environment. Gyroscopic forces are utilized for defining the collision avoidance control strategy: This kind of forces leads to avoiding collisions, without interfering with the convergence properties of the multi-robot system’s desired control law. Collision avoidance introduces, in fact, a perturbation on the nominal behavior of the system: We define a method for choosing the direction of the gyroscopic force in an optimal manner, in such a way that perturbation is minimized. Collision avoidance and convergence properties are analytically demonstrated, and simulation results are provided for validation purpose.

  8. Information-flux approach to multiple-spin dynamics

    Science.gov (United States)

    di Franco, C.; Paternostro, M.; Palma, G. M.; Kim, M. S.

    2007-10-01

    We introduce and formalize the concept of information flux in a many-body register as the influence that the dynamics of a specific element receive from any other element of the register. By quantifying the information flux in a protocol, we can design the most appropriate initial state of the system and, noticeably, the distribution of coupling strengths among the parts of the register itself. The intuitive nature of this tool and its flexibility, which allow for easily manageable numerical approaches when analytic expressions are not straightforward, are greatly useful in interacting many-body systems such as quantum spin chains. We illustrate the use of this concept in quantum cloning and quantum state transfer and we also sketch its extension to nonunitary dynamics.

  9. Dynamic Resource Allocation for Multiple-Antenna Wireless Power Transfer

    OpenAIRE

    Yang, Gang; Ho, Chin Keong; Guan, Yong Liang

    2013-01-01

    We consider a point-to-point multiple-input-single-output (MISO) system where a receiver harvests energy from a wireless power transmitter to power itself for various applications. The transmitter performs energy beamforming by using an instantaneous channel state information (CSI). The CSI is estimated at the receiver by training via a preamble, and fed back to the transmitter. The channel estimate is more accurate when longer preamble is used, but less time is left for wireless power transf...

  10. Dynamic regulation of aquaporin-4 water channels in neurological disorders

    Science.gov (United States)

    Hsu, Ying; Tran, Minh; Linninger, Andreas A.

    2015-01-01

    Aquaporin-4 water channels play a central role in brain water regulation in neurological disorders. Aquaporin-4 is abundantly expressed at the astroglial endfeet facing the cerebral vasculature and the pial membrane, and both its expression level and subcellular localization significantly influence brain water transport. However, measurements of aquaporin-4 levels in animal models of brain injury often report opposite trends of change at the injury core and the penumbra. Furthermore, aquaporin-4 channels play a beneficial role in brain water clearance in vasogenic edema, but a detrimental role in cytotoxic edema and exacerbate cell swelling. In light of current evidence, we still do not have a complete understanding of the role of aquaporin-4 in brain water transport. In this review, we propose that the regulatory mechanisms of aquaporin-4 at the transcriptional, translational, and post-translational levels jointly regulate water permeability in the short and long time scale after injury. Furthermore, in order to understand why aquaporin-4 channels play opposing roles in cytotoxic and vasogenic edema, we discuss experimental evidence on the dynamically changing osmotic gradients between blood, extracellular space, and the cytosol during the formation of cytotoxic and vasogenic edema. We conclude with an emerging picture of the distinct osmotic environments in cytotoxic and vasogenic edema, and propose that the directions of aquaporin-4-mediated water clearance in these two types of edema are distinct. The difference in water clearance pathways may provide an explanation for the conflicting observations of the roles of aquaporin-4 in edema resolution. PMID:26526878

  11. Multi-Equilibria Regulation Agent-Based Model of Opinion Dynamics in Social Networks

    Directory of Open Access Journals (Sweden)

    Andreas Koulouris

    2013-01-01

    Full Text Available This article investigates the Multiple Equilibria Regulation (MER model, i.e., an agent-based simulation model, to represent opinion dynamics in social networks. It relies on a small set of micro-prerequisites (intra-individual balance and confidence bound, leading to emergence of (nonstationary macro-outcomes. These outcomes may refer to consensus, polarization or fragmentation of opinions about taxation (e.g., congestion pricing or other policy measures, according to the way communication is structured. In contrast with other models of opinion dynamics, it allows for the impact of both the regulation of intra-personal discrepancy and the interpersonal variability of opinions on social learning and network dynamics. Several simulation experiments are presented to demonstrate, through the MER model, the role of different network structures (complete, star, cellular automata, small-world and random graphs on opinion formation dynamics and the overall evolution of the system. The findings can help to identify specific topological characteristics, such as density, number of neighbourhoods and critical nodes-agents, that affect the stability and system dynamics. This knowledge can be used to better organize the information diffusion and learning in the community, enhance the predictability of outcomes and manage possible conflicts. It is shown that a small-world organization, which depicts more realistic aspects of real-life and virtual social systems, provides increased predictability and stability towards a less fragmented and more manageable grouping of opinions, compared to random networks. Such macro-level organizations may be enhanced with use of web-based technologies to increase the density of communication and public acceptability of policy measures.

  12. Modelling the Dynamics of Intracellular Processes as an Organisation of Multiple Agents

    NARCIS (Netherlands)

    Bosse, T.; Jonker, C.M.; Treur, J.; Armano, G.; Merelli, E.; Denzinger, J.; Martin, A.; Miles, S.; Tianfield, H.; Unland, R.

    2005-01-01

    This paper explores how the dynamics of complex biological processes can be modeled as an organisation of multiple agents. This modelling perspective identifies organisational structure occurring in complex decentralised processes and handles complexity of the analysis of the dynamics by structuring

  13. Dynamics of the Greenland Ice Sheet over multiple timescales

    DEFF Research Database (Denmark)

    Kjeldsen, Kristian Kjellerup

    Since the 1990s mass loss of the Greenland Ice Sheet has accelerated substantially increasing its contribution to global sea level rise, especially during the past decade. Even though the current global sea level budget is well understood, providing better estimates of the mass loss is essential...... that the ice margin of the Greenland Ice Sheet responds highly dynamic and variable to climate change and oceanic forcing, with behavior additionally being governed by regional/local settings, e.g. topographical settings such as low-lying/mountainous areas and the presence or absence of deep fjords or shelf...

  14. Dynamic information architecture system (DIAS) : multiple model simulation management.

    Energy Technology Data Exchange (ETDEWEB)

    Simunich, K. L.; Sydelko, P.; Dolph, J.; Christiansen, J.

    2002-05-13

    Dynamic Information Architecture System (DIAS) is a flexible, extensible, object-based framework for developing and maintaining complex multidisciplinary simulations of a wide variety of application contexts. The modeling domain of a specific DIAS-based simulation is determined by (1) software Entity (domain-specific) objects that represent the real-world entities that comprise the problem space (atmosphere, watershed, human), and (2) simulation models and other data processing applications that express the dynamic behaviors of the domain entities. In DIAS, models communicate only with Entity objects, never with each other. Each Entity object has a number of Parameter and Aspect (of behavior) objects associated with it. The Parameter objects contain the state properties of the Entity object. The Aspect objects represent the behaviors of the Entity object and how it interacts with other objects. DIAS extends the ''Object'' paradigm by abstraction of the object's dynamic behaviors, separating the ''WHAT'' from the ''HOW.'' DIAS object class definitions contain an abstract description of the various aspects of the object's behavior (the WHAT), but no implementation details (the HOW). Separate DIAS models/applications carry the implementation of object behaviors (the HOW). Any model deemed appropriate, including existing legacy-type models written in other languages, can drive entity object behavior. The DIAS design promotes plug-and-play of alternative models, with minimal recoding of existing applications. The DIAS Context Builder object builds a constructs or scenario for the simulation, based on developer specification and user inputs. Because DIAS is a discrete event simulation system, there is a Simulation Manager object with which all events are processed. Any class that registers to receive events must implement an event handler (method) to process the event during execution. Event handlers

  15. Dynamic information architecture system (DIAS) : multiple model simulation management

    International Nuclear Information System (INIS)

    Simunich, K. L.; Sydelko, P.; Dolph, J.; Christiansen, J.

    2002-01-01

    Dynamic Information Architecture System (DIAS) is a flexible, extensible, object-based framework for developing and maintaining complex multidisciplinary simulations of a wide variety of application contexts. The modeling domain of a specific DIAS-based simulation is determined by (1) software Entity (domain-specific) objects that represent the real-world entities that comprise the problem space (atmosphere, watershed, human), and (2) simulation models and other data processing applications that express the dynamic behaviors of the domain entities. In DIAS, models communicate only with Entity objects, never with each other. Each Entity object has a number of Parameter and Aspect (of behavior) objects associated with it. The Parameter objects contain the state properties of the Entity object. The Aspect objects represent the behaviors of the Entity object and how it interacts with other objects. DIAS extends the ''Object'' paradigm by abstraction of the object's dynamic behaviors, separating the ''WHAT'' from the ''HOW.'' DIAS object class definitions contain an abstract description of the various aspects of the object's behavior (the WHAT), but no implementation details (the HOW). Separate DIAS models/applications carry the implementation of object behaviors (the HOW). Any model deemed appropriate, including existing legacy-type models written in other languages, can drive entity object behavior. The DIAS design promotes plug-and-play of alternative models, with minimal recoding of existing applications. The DIAS Context Builder object builds a constructs or scenario for the simulation, based on developer specification and user inputs. Because DIAS is a discrete event simulation system, there is a Simulation Manager object with which all events are processed. Any class that registers to receive events must implement an event handler (method) to process the event during execution. Event handlers can schedule other events; create or remove Entities from the

  16. Dynamics of the Greenland Ice Sheet over multiple timescales

    DEFF Research Database (Denmark)

    Kjeldsen, Kristian Kjellerup

    Since the 1990s mass loss of the Greenland Ice Sheet has accelerated substantially increasing its contribution to global sea level rise, especially during the past decade. Even though the current global sea level budget is well understood, providing better estimates of the mass loss is essential....../crossshelf troughs. Warming of ocean temperatures is suggested as being a main driver for periodic dynamic ice loss events in northwest Greenland while cooling of ocean temperatures around southern Greenland, in conjunction with increased snow accumulation, is found to drive a rapid readvance of glaciers in response...... to the onset of the Little Ice Age. Furthermore this thesis shows that the thinning pattern of the last decade in southern Greenland compares well with that of the entire 20th century, thus the present sensitivity distribution will arguably hold for future ice sheet mass loss until marine outlet glaciers...

  17. A DYNAMICAL SIGNATURE OF MULTIPLE STELLAR POPULATIONS IN 47 TUCANAE

    International Nuclear Information System (INIS)

    Richer, Harvey B.; Heyl, Jeremy; Anderson, Jay; Kalirai, Jason S.; Shara, Michael M.; Dotter, Aaron; Fahlman, Gregory G.; Rich, R. Michael

    2013-01-01

    Based on the width of its main sequence, and an actual observed split when viewed through particular filters, it is widely accepted that 47 Tucanae contains multiple stellar populations. In this contribution, we divide the main sequence of 47 Tuc into four color groups, which presumably represent stars of various chemical compositions. The kinematic properties of each of these groups are explored via proper motions, and a strong signal emerges of differing proper-motion anisotropies with differing main-sequence color; the bluest main-sequence stars exhibit the largest proper-motion anisotropy which becomes undetectable for the reddest stars. In addition, the bluest stars are also the most centrally concentrated. A similar analysis for Small Magellanic Cloud stars, which are located in the background of 47 Tuc on our frames, yields none of the anisotropy exhibited by the 47 Tuc stars. We discuss implications of these results for possible formation scenarios of the various populations.

  18. Multiple ionization dynamics of molecules in intense laser fields

    International Nuclear Information System (INIS)

    Ichimura, Atsushi; Ohyama-Yamaguchi, Tomoko

    2005-01-01

    A classical field-ionization model is developed for sequential multiple ionization of diatomic and linear triatomic molecules exposed to intense (∼ 10 15 W/cm 2 ) laser fields. The distance R ion of Coulomb explosion is calculated for a combination of fragment charges, by considering nonadiabatic excitation followed by field ionization associated with the inner and outer saddle points. For diatomic molecules (N 2 , NO, and I 2 ), the model explains behaviors observed in experiments, as R ion (21→31) ion (21→22) between competing charge-asymmetric and symmetric channels, and even-odd fluctuation along a principal pathway. For a triatomic molecule CO 2 , a comparison of the model with an experiment suggests that charge-symmetric (or nearly symmetric) channels are dominantly populated. (author)

  19. Evaluating sustainability of truck weight regulations: A system dynamics view

    Directory of Open Access Journals (Sweden)

    Pei Liu

    2015-11-01

    Full Text Available Purpose: Targeting the problem of overload trucking in Highway Transportation of iron ore from Caofeidian to Tangshan (HTCT, this paper aims to assess long-term effects of alternative Truck Weight Regulation (TWR policies on sustainability of HTCT. Design/methodology/approach: A system dynamics model was established for policy evaluation. The model, composed of six interrelating modules, is able to simulate policies effects on trucking issues such as freight flow, truck traffic flow, pavement performance, highway transport capacity and trucking time, and further on the Cumulative Economic Cost (CEC including transport cost and time cost of freight owners and the Cumulative Social Cost (CSC including pavement maintenance cost, green house gas emission cost, air pollutants emission cost and traffic accidents cost, so the effects of TWR policies on sustainability of HTCT could be evaluated. Findings: According to different values of overload ratio which a TWR policy allows, alternative TWR policies are classified into three types, which are The Rigid Policy (TRP, The Moderate Policy (TMP and The Tolerant Policy (TTP. Results show that the best policy for sustainability of HTCT depends on the importance of CSC which is expected by the local government. To be specific, (1 if CSC is considered much less important than CEC, the local government should continue implementing the current TTP with the maximum overload ratio; (2 if CSC is considered much more important than CEC, then TRP is recommended; and (3 if CSC is considered slightly more important than CES, TMP with overload ratio of 80% is the best. Practical implications: Conclusions of this paper may help the local government design appropriate TWR policies to achieve sustainability of HTCT. Originality/value: To the best of our knowledge, this is the first effort to evaluate TWR policies on sustainability of regional freight transportation based on system dynamics modeling.

  20. Dynamics of adenylate cyclase regulation via heterotrimeric G-proteins.

    Science.gov (United States)

    Milde, Markus; Werthmann, Ruth C; von Hayn, Kathrin; Bünemann, Moritz

    2014-04-01

    A wide variety of G-protein-coupled receptors either activate or inhibit ACs (adenylate cyclases), thereby regulating cellular cAMP levels and consequently inducing proper physiological responses. Stimulatory and inhibitory G-proteins interact directly with ACs, whereas G(q)-coupled receptors exert their effects primarily via Ca2+. Using the FRET-based cAMP sensor Epac1 (exchange protein directly activated by cAMP 1)-cAMPS (adenosine 3',5'-cyclic monophosphorothioate), we studied cAMP levels in single living VSMCs (vascular smooth muscle cells) or HUVECs (human umbilical vein endothelial cells) with subsecond temporal resolution. Stimulation of purinergic (VSMCs) or thrombin (HUVECs) receptors rapidly decreased cAMP levels in the presence of the β-adrenergic agonist isoprenaline via a rise in Ca2+ and subsequent inhibition of AC5 and AC6. Specifically in HUVECs, we observed that, in the continuous presence of thrombin, cAMP levels climbed slowly after the initial decline with a delay of a little less than 1 min. The underlying mechanism includes phospholipase A2 activity and cyclo-oxygenase-mediated synthesis of prostaglandins. We studied further the dynamics of the inhibition of ACs via G(i)-proteins utilizing FRET imaging to resolve interactions between fluorescently labelled G(i)-proteins and AC5. FRET between Gα(i1) and AC5 developed at much lower concentration of agonist compared with the overall G(i)-protein activity. We found the dissociation of Gα(i1) subunits and AC5 to occur slower than the G(i)-protein deactivation. This led us to the conclusion that AC5, by binding active Gα(i1), interferes with G-protein deactivation and reassembly and thereby might sensitize its own regulation.

  1. MicroRNA: Dynamic Regulators of Macrophage Polarization and Plasticity

    Directory of Open Access Journals (Sweden)

    Jezrom Bokcaerin Self-Fordham

    2017-08-01

    Full Text Available The ability of a healthy immune system to clear the plethora of antigens it encounters incessantly relies on the enormous plasticity displayed by the comprising cell types. Macrophages (MΦs are crucial member of the mononuclear phagocyte system (MPS that constantly patrol the peripheral tissues and are actively recruited to the sites of injury and infection. In tissues, infiltrating monocytes replenish MΦ. Under the guidance of the local micro-milieu, MΦ can be activated to acquire specialized functional phenotypes. Similar to T cells, functional polarization of macrophage phenotype viz., inflammatory (M1 and reparative (M2 is proposed. Equipped with diverse toll-like receptors (TLRs, these cells of the innate arm of immunity recognize and phagocytize antigens and secrete cytokines that activate the adaptive arm of the immune system and perform key roles in wound repair. Dysregulation of MΦ plasticity has been associated with various diseases and infection. MicroRNAs (miRNAs have emerged as critical regulators of transcriptome output. Their importance in maintaining health, and their contribution toward disease, encompasses virtually all aspects of human biology. Our understanding of miRNA-mediated regulation of MΦ plasticity and polarization can be utilized to modulate functional phenotypes to counter their role in the pathogenesis of numerous disease, including cancer, autoimmunity, periodontitis, etc. Here, we provide an overview of current knowledge regarding the role of miRNA in shaping MΦ polarization and plasticity through targeting of various pathways and genes. Identification of miRNA biomarkers of diagnostic/prognostic value and their therapeutic potential by delivery of miRNA mimics or inhibitors to dynamically alter gene expression profiles in vivo is highlighted.

  2. Dynamic regulation of Drosophila nuclear receptor activity in vivo.

    Science.gov (United States)

    Palanker, Laura; Necakov, Aleksandar S; Sampson, Heidi M; Ni, Ruoyu; Hu, Chun; Thummel, Carl S; Krause, Henry M

    2006-09-01

    Nuclear receptors are a large family of transcription factors that play major roles in development, metamorphosis, metabolism and disease. To determine how, where and when nuclear receptors are regulated by small chemical ligands and/or protein partners, we have used a 'ligand sensor' system to visualize spatial activity patterns for each of the 18 Drosophila nuclear receptors in live developing animals. Transgenic lines were established that express the ligand binding domain of each nuclear receptor fused to the DNA-binding domain of yeast GAL4. When combined with a GAL4-responsive reporter gene, the fusion proteins show tissue- and stage-specific patterns of activation. We show that these responses accurately reflect the presence of endogenous and exogenously added hormone, and that they can be modulated by nuclear receptor partner proteins. The amnioserosa, yolk, midgut and fat body, which play major roles in lipid storage, metabolism and developmental timing, were identified as frequent sites of nuclear receptor activity. We also see dynamic changes in activation that are indicative of sweeping changes in ligand and/or co-factor production. The screening of a small compound library using this system identified the angular psoralen angelicin and the insect growth regulator fenoxycarb as activators of the Ultraspiracle (USP) ligand-binding domain. These results demonstrate the utility of this system for the functional dissection of nuclear receptor pathways and for the development of new receptor agonists and antagonists that can be used to modulate metabolism and disease and to develop more effective means of insect control.

  3. Transitions between multiple equilibria of paleo climate: a glimpse in to the dynamics of abrupt climate change

    Science.gov (United States)

    Ferreira, David; Marshall, John; Ito, Takamitsu; McGee, David; Moreno-Chamarro, Eduardo

    2017-04-01

    The dynamics regulating large climatic transitions such as glacial-interglacial cycles or DO events remains a puzzle. Forcings behind these transitions are not robustly identified and potential candidates (e.g. Milankovitch cycles, freshwater perturbations) often appear too weak to explain such dramatic transitions. A potential solution to this long-standing puzzle is that Earth's climate is endowed with multiple equilibrium states of global extent. Such states are commonly found in low-order or conceptual climate models, but it is unclear whether a system as complex as Earth's climate can sustain multiple equilibrium states. Here we report that multiple equilibrium states of the climate system are also possible in a complex, fully dynamical coupled ocean-atmosphere-sea ice GCM with idealized Earth-like geometry, resolved weather systems and a hydrological cycle. In our model, two equilibrium states coexist for the same parameters and external forcings: a Warm climate with a small Northern hemisphere sea ice cap and a large southern one and a Cold climate with large ice caps at both poles. The dynamical states of the Warm and Cold solutions exhibit striking similarities with our present-day climate and the climate of the Last Glacial Maximum, respectively. A carbon cycle model driven by the two dynamical states produces an atmospheric pCO2 draw-down of about 110 pm between the Warm and Cold states, close to Glacial-Interglacial differences found in ice cores. Mechanism controlling the existence of the multiple states and changes in the atmospheric CO2 will be briefly presented. Finally we willdescribe transition experiments from the Cold to the Warm state, focusing on the lead-lags in the system, notably between the Northern and Southern Hemispheres climates.

  4. Tension regulates myosin dynamics during Drosophila embryonic wound repair.

    Science.gov (United States)

    Kobb, Anna B; Zulueta-Coarasa, Teresa; Fernandez-Gonzalez, Rodrigo

    2017-02-15

    Embryos repair epithelial wounds rapidly in a process driven by collective cell movements. Upon wounding, actin and the molecular motor non-muscle myosin II are redistributed in the cells adjacent to the wound, forming a supracellular purse string around the lesion. Purse string contraction coordinates cell movements and drives rapid wound closure. By using fluorescence recovery after photobleaching in Drosophila embryos, we found that myosin turns over as the purse string contracts. Myosin turnover at the purse string was slower than in other actomyosin networks that had a lower level of contractility. Mathematical modelling suggested that myosin assembly and disassembly rates were both reduced by tension at the wound edge. We used laser ablation to show that tension at the purse string increased as wound closure progressed, and that the increase in tension was associated with reduced myosin turnover. Reducing purse string tension by laser-mediated severing resulted in increased turnover and loss of myosin. Finally, myosin motor activity was necessary for its stabilization around the wound and for rapid wound closure. Our results indicate that mechanical forces regulate myosin dynamics during embryonic wound repair. © 2017. Published by The Company of Biologists Ltd.

  5. Revealing Pathway Dynamics in Heart Diseases by Analyzing Multiple Differential Networks.

    Directory of Open Access Journals (Sweden)

    Xiaoke Ma

    2015-06-01

    Full Text Available Development of heart diseases is driven by dynamic changes in both the activity and connectivity of gene pathways. Understanding these dynamic events is critical for understanding pathogenic mechanisms and development of effective treatment. Currently, there is a lack of computational methods that enable analysis of multiple gene networks, each of which exhibits differential activity compared to the network of the baseline/healthy condition. We describe the iMDM algorithm to identify both unique and shared gene modules across multiple differential co-expression networks, termed M-DMs (multiple differential modules. We applied iMDM to a time-course RNA-Seq dataset generated using a murine heart failure model generated on two genotypes. We showed that iMDM achieves higher accuracy in inferring gene modules compared to using single or multiple co-expression networks. We found that condition-specific M-DMs exhibit differential activities, mediate different biological processes, and are enriched for genes with known cardiovascular phenotypes. By analyzing M-DMs that are present in multiple conditions, we revealed dynamic changes in pathway activity and connectivity across heart failure conditions. We further showed that module dynamics were correlated with the dynamics of disease phenotypes during the development of heart failure. Thus, pathway dynamics is a powerful measure for understanding pathogenesis. iMDM provides a principled way to dissect the dynamics of gene pathways and its relationship to the dynamics of disease phenotype. With the exponential growth of omics data, our method can aid in generating systems-level insights into disease progression.

  6. Long-Timescale Dynamics and Regulation of Sec-Facilitated Protein Translocation

    Directory of Open Access Journals (Sweden)

    Bin Zhang

    2012-10-01

    Full Text Available We present a coarse-grained modeling approach that spans the nanosecond- to minute-timescale dynamics of cotranslational protein translocation. The method enables direct simulation of both integral membrane protein topogenesis and transmembrane domain (TM stop-transfer efficiency. Simulations reveal multiple kinetic pathways for protein integration, including a mechanism in which the nascent protein undergoes slow-timescale reorientation, or flipping, in the confined environment of the translocon channel. Competition among these pathways gives rise to the experimentally observed dependence of protein topology on ribosomal translation rate and protein length. We further demonstrate that sigmoidal dependence of stop-transfer efficiency on TM hydrophobicity arises from local equilibration of the TM across the translocon lateral gate, and it is predicted that slowing ribosomal translation yields decreased stop-transfer efficiency in long proteins. This work reveals the balance between equilibrium and nonequilibrium processes in protein targeting, and it provides insight into the molecular regulation of the Sec translocon.

  7. Dynamics of Bayesian non-Gaussian sensorimotor learning with multiple time scales

    Science.gov (United States)

    Zhou, Baohua; Hofmann, David; Sober, Samuel; Nemenman, Ilya

    Various theoretical and experimental studies have suggested that sensorimotor learning in animals happens on multiple time scales. In such models, animals can respond to perturbations quickly but keep memories for a long period of time. However, those previous models only focus on average learning behaviors. Here, we propose a model with multiple time scales that deals with the dynamics of whole behavior distributions. The model includes multiple memories, each with a non-Gaussian distribution and its own associated time scale. The memories are combined to generate a distribution of the desired motor command. Our model explains simultaneously the dynamics of distributions of the songbird vocal behaviors in various experiments, including adaptations after step changes or ramps in the error signals and dynamics of forgetting during the washout period, where an immediate sharp approach to the baseline is followed by a prolonged decay. This work was supported partially by NIH Grant # 1 R01 EB022872, and NIH Grant # NS084844.

  8. Generating Gaits for Biped Robots Using Multiple Dynamic Passivization of Joint Control

    Science.gov (United States)

    Ishida, Minoru; Kato, Shohei; Kanoh, Masayoshi; Itoh, Hidenori

    In the research field of bipedal locomotion, a central pattern generator (CPG) and passive dynamic walking (PDW) have attracted much attention. In this paper, we describe a motion control system for biped robots based on dynamic joint passivization. Our motion control system is based on a mixture of the CPG and PDW, that is, the multiple dynamic passivization of joint control (MDPJC). Our intention is to make the joint control of the swing leg temporarily passive in the swing leg phase. The important part is the passive phase time and the switch timings of the joint control. We optimize the switch timing parameters using simulated annealing with advanced adaptive neighborhood (SA/AAN). Experiments using the motion control system based on multiple dynamic passivization of joint control successfully generated energy efficient walking and enabled superior gaits.

  9. Pathways to positivity from perceived stress in adolescents: multiple mediation of emotion regulation and coping strategies

    Directory of Open Access Journals (Sweden)

    Mehmet Ali Yildiz

    2017-05-01

    Full Text Available Background The current study aimed to examine the multiple mediation of emotion regulation and coping strategies in the relationship between perceived stress and positivity in adolescents. Participants and procedure Participants included 312 adolescents attending high schools. 162 of the participants were female and 150 were male, with an average age of 16.26, SD = 1.21. Data collection was conducted with the Perceived Stress Scale, the Emotion Regulation Scale for Adolescents, the Coping Scale for Children and Youth, and the Positivity Scale. Descriptive statistics, Pearson’s correlation coefficient, regression based on ordinary least squares, and the bootstrap method were used to analyze the research data. Results The research findings indicated that internal dysfunctional emotion regulation, assistance seeking, problem solving, and behavioral avoidance mediated the relationship between perceived stress and positivity. Conclusion In conclusion, internal dysfunctional emotion regulation, seeking assistance, problem solving, and behavioral avoidance were found to mediate the relationship between adolescents’ perceived stress and positivity. Thus, preparing individual and group psychological counseling as well as emotion regulation and coping-oriented psycho-educational programs for adolescents to regulate negative emotions and to cope with stress may be important. The research findings were discussed and interpreted based on the relevant literature, and suggestions for relevant experts were included.

  10. Functional adaptation to loading of a single bone is neuronally regulated and involves multiple bones.

    Science.gov (United States)

    Sample, Susannah J; Behan, Mary; Smith, Lesley; Oldenhoff, William E; Markel, Mark D; Kalscheur, Vicki L; Hao, Zhengling; Miletic, Vjekoslav; Muir, Peter

    2008-09-01

    Regulation of load-induced bone formation is considered a local phenomenon controlled by osteocytes, although it has also been hypothesized that functional adaptation may be neuronally regulated. The aim of this study was to examine bone formation in multiple bones, in response to loading of a single bone, and to determine whether adaptation may be neuronally regulated. Load-induced responses in the left and right ulnas and humeri were determined after loading of the right ulna in male Sprague-Dawley rats (69 +/- 16 days of age). After a single period of loading at -760-, -2000-, or -3750-microepsilon initial peak strain, rats were given calcein to label new bone formation. Bone formation and bone neuropeptide concentrations were determined at 10 days. In one group, temporary neuronal blocking was achieved by perineural anesthesia of the brachial plexus with bupivicaine during loading. We found right ulna loading induces adaptive responses in other bones in both thoracic limbs compared with Sham controls and that neuronal blocking during loading abrogated bone formation in the loaded ulna and other thoracic limb bones. Skeletal adaptation was more evident in distal long bones compared with proximal long bones. We also found that the single period of loading modulated bone neuropeptide concentrations persistently for 10 days. We conclude that functional adaptation to loading of a single bone in young rapidly growing rats is neuronally regulated and involves multiple bones. Persistent changes in bone neuropeptide concentrations after a single loading period suggest that plasticity exists in the innervation of bone.

  11. Multiple diguanylate cyclase-coordinated regulation of pyoverdine synthesis in Pseudomonas aeruginosa

    DEFF Research Database (Denmark)

    Chen, Yicai; Yuan, Mingjun; Mohanty, Anee

    2015-01-01

    intrinsic feature of c-di-GMP signalling is the abundance of DGCs and PDEs encoded by many bacterial species. It is unclear whether the different DGCs or PDEs coordinately establish the c-di-GMP regulation or function independently of each other. Here, we provide evidence that multiple DGCs are involved......The nucleotide signalling molecule bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP) plays an essential role in regulating microbial virulence and biofilm formation. C-di-GMP is synthesized by diguanylate cyclase (DGC) enzymes and degraded by phosphodiesterase (PDE) enzymes. One...... in regulation of c-di-GMP on synthesis of the major iron siderophore pyoverdine in Pseudomonas aeruginosa. Constitutive expression of the WspG or YedQ DGC in P.aeruginosa is able to induce its pyoverdine synthesis. Induction of pyoverdine synthesis by high intracellular c-di-GMP depends on the synthesis...

  12. Parameter Effects and Solving Linear Equations in Dynamic, Linked, Multiple Representation Environments.

    Science.gov (United States)

    Lin, Pao-Ping; Hsieh, Che-Jen

    1993-01-01

    Describes the Geometer's Sketchpad, a geometric construction kit composed of three manipulatable, dynamic, linked, multiple representation environments: the coordinate system, formulas, and graphs. Examines the use of the environments for studying parameter effects of linear and quadratic functions and for solving linear equations. (MDH)

  13. Moral motivation based on multiple developmental structures: an exploration of cognitive and emotional dynamics.

    Science.gov (United States)

    Kaplan, Ulas; Tivnan, Terrence

    2014-01-01

    Intrapersonal variability and multiplicity in the complexity of moral motivation were examined from Dynamic Systems and Self-Determination Theory perspectives. L. Kohlberg's (1969) stages of moral development are reconceptualized as soft-assembled and dynamically transformable process structures of motivation that may operate simultaneously within person in different degrees. Moral motivation is conceptualized as the real-time process of self-organization of cognitive and emotional dynamics out of which moral judgment and action emerge. A detailed inquiry into intrapersonal variation in moral motivation is carried out based on the differential operation of multiple motivational structures. A total of 74 high school students and 97 college students participated in the study by completing a new questionnaire, involving 3 different hypothetical moral judgments. As hypothesized, findings revealed significant multiplicity in the within-person operation of developmental stage structures, and intrapersonal variability in the degrees to which stages were used. Developmental patterns were found in terms of different distributions of multiple stages between high school and college samples, as well as the association between age and overall motivation scores. Differential relations of specific emotions to moral motivation revealed and confirmed the value of differentiating multiple emotions. Implications of the present theoretical perspective and the findings for understanding the complexity of moral judgment and motivation are discussed.

  14. Modeling Adaptive Dynamical Systems to Analyze Eating Regulation Disorders

    NARCIS (Netherlands)

    Bosse, T.; Delfos, M.F.; Jonker, C.M.; Treur, J.

    2006-01-01

    To analyze the disorders of their patients, psychotherapists often have to get insight in adaptive dynamical systems. Analysis of dynamical systems usually is performed using mathematical techniques. Such an analysis is not precisely the type of reasoning performed in psychotherapy practice. In this

  15. Tag team: Roles of miRNAs and Proteolytic Regulators in Ensuring Robust Gene Expression Dynamics.

    Science.gov (United States)

    Weaver, Benjamin P; Han, Min

    2018-01-01

    Lack of prominent developmental defects arising from loss of many individual miRNAs is consistent with the observations of collaborative networks between miRNAs and roles for miRNAs in regulating stress responses. However, these characteristics may only partially explain the seemingly nonessential nature of many miRNAs. Non-miRNA gene expression regulatory mechanisms also collaborate with miRNA-induced silencing complex (miRISC) to support robust gene expression dynamics. Genetic enhancer screens have revealed roles of miRNAs and other gene repressive mechanisms in development or other cellular processes that were masked by genetic redundancy. Besides discussing the breadth of the non-miRNA genes, we use LIN-28 as an example to illustrate how distinct regulatory systems, including miRNAs and multiple protein stability mechanisms, work at different levels to target expression of a given gene and provide tissue-specific and stage-specific regulation of gene expression. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Dynamic Water Regulation Under Endogenous Irrigation Investment and Production Uncertainty

    OpenAIRE

    Zhang, Jiangfeng

    2001-01-01

    We study the problem of regulating California agriculture water use. Regulatory decisions are conditioned on current information as well as the anticipation of future learning. Endogenous learning, either about damages from waterlogging or about abatement costs, affects the optimal control today. These regulations affect farmers' water usage and their incentives to adopt new irrigation technology.

  17. An evaluation of biosurveillance grid--dynamic algorithm distribution across multiple computer nodes.

    Science.gov (United States)

    Tsai, Ming-Chi; Tsui, Fu-Chiang; Wagner, Michael M

    2007-10-11

    Performing fast data analysis to detect disease outbreaks plays a critical role in real-time biosurveillance. In this paper, we described and evaluated an Algorithm Distribution Manager Service (ADMS) based on grid technologies, which dynamically partition and distribute detection algorithms across multiple computers. We compared the execution time to perform the analysis on a single computer and on a grid network (3 computing nodes) with and without using dynamic algorithm distribution. We found that algorithms with long runtime completed approximately three times earlier in distributed environment than in a single computer while short runtime algorithms performed worse in distributed environment. A dynamic algorithm distribution approach also performed better than static algorithm distribution approach. This pilot study shows a great potential to reduce lengthy analysis time through dynamic algorithm partitioning and parallel processing, and provides the opportunity of distributing algorithms from a client to remote computers in a grid network.

  18. An Evaluation of Biosurveillance Grid—Dynamic Algorithm Distribution Across Multiple Computer Nodes

    Science.gov (United States)

    Tsai, Ming-Chi; Tsui, Fu-Chiang; Wagner, Michael M.

    2007-01-01

    Performing fast data analysis to detect disease outbreaks plays a critical role in real-time biosurveillance. In this paper, we described and evaluated an Algorithm Distribution Manager Service (ADMS) based on grid technologies, which dynamically partition and distribute detection algorithms across multiple computers. We compared the execution time to perform the analysis on a single computer and on a grid network (3 computing nodes) with and without using dynamic algorithm distribution. We found that algorithms with long runtime completed approximately three times earlier in distributed environment than in a single computer while short runtime algorithms performed worse in distributed environment. A dynamic algorithm distribution approach also performed better than static algorithm distribution approach. This pilot study shows a great potential to reduce lengthy analysis time through dynamic algorithm partitioning and parallel processing, and provides the opportunity of distributing algorithms from a client to remote computers in a grid network. PMID:18693936

  19. Dynamic Bus Travel Time Prediction Models on Road with Multiple Bus Routes.

    Science.gov (United States)

    Bai, Cong; Peng, Zhong-Ren; Lu, Qing-Chang; Sun, Jian

    2015-01-01

    Accurate and real-time travel time information for buses can help passengers better plan their trips and minimize waiting times. A dynamic travel time prediction model for buses addressing the cases on road with multiple bus routes is proposed in this paper, based on support vector machines (SVMs) and Kalman filtering-based algorithm. In the proposed model, the well-trained SVM model predicts the baseline bus travel times from the historical bus trip data; the Kalman filtering-based dynamic algorithm can adjust bus travel times with the latest bus operation information and the estimated baseline travel times. The performance of the proposed dynamic model is validated with the real-world data on road with multiple bus routes in Shenzhen, China. The results show that the proposed dynamic model is feasible and applicable for bus travel time prediction and has the best prediction performance among all the five models proposed in the study in terms of prediction accuracy on road with multiple bus routes.

  20. Dynamic Bus Travel Time Prediction Models on Road with Multiple Bus Routes

    Science.gov (United States)

    Bai, Cong; Peng, Zhong-Ren; Lu, Qing-Chang; Sun, Jian

    2015-01-01

    Accurate and real-time travel time information for buses can help passengers better plan their trips and minimize waiting times. A dynamic travel time prediction model for buses addressing the cases on road with multiple bus routes is proposed in this paper, based on support vector machines (SVMs) and Kalman filtering-based algorithm. In the proposed model, the well-trained SVM model predicts the baseline bus travel times from the historical bus trip data; the Kalman filtering-based dynamic algorithm can adjust bus travel times with the latest bus operation information and the estimated baseline travel times. The performance of the proposed dynamic model is validated with the real-world data on road with multiple bus routes in Shenzhen, China. The results show that the proposed dynamic model is feasible and applicable for bus travel time prediction and has the best prediction performance among all the five models proposed in the study in terms of prediction accuracy on road with multiple bus routes. PMID:26294903

  1. Frequency Splitting Elimination and Cross-Coupling Rejection of Wireless Power Transfer to Multiple Dynamic Receivers

    Directory of Open Access Journals (Sweden)

    Narayanamoorthi R.

    2018-01-01

    Full Text Available Simultaneous power transfer to multiple receiver (Rx system is one of the key advantages of wireless power transfer (WPT system using magnetic resonance. However, determining the optimal condition to uniformly transfer the power to a selected Rx at high efficiency is the challenging task under the dynamic environment. The cross-coupling and frequency splitting are the dominant issues present in the multiple Rx dynamic WPT system. The existing analysis is performed by considering any one issue present in the system; on the other hand, the cross coupling and frequency splitting issues are interrelated in dynamic Rx’s, which requires a comprehensive design strategy by considering both the problems. This paper proposes an optimal design of multiple Rx WPT system, which can eliminate cross coupling, frequency splitting issues and increase the power transfer efficiency (PTE of selected Rx. The cross-coupling rejection, uniform power transfer is performed by adding an additional relay coil and independent resonance frequency tuning with capacitive compensation to each Rx unit. The frequency splitting phenomena are eliminated using non-identical transmitter (Tx and Rx coil structure which can maintain the coupling between the coil under the critical coupling limit. The mathematical analysis of the compensation capacitance calculation and optimal Tx coil size identification is performed for the four Rx WPT system. Finite element analysis and experimental investigation are carried out for the proposed design in static and dynamic conditions.

  2. IVF policy and global/local politics: the making of multiple-embryo transfer regulation in Taiwan.

    Science.gov (United States)

    Wu, Chia-Ling

    2012-08-01

    This paper analyzes the regulatory trajectory of multiple-embryo transfer in in-vitro fertilization (IVF) in Taiwan. Taking a latecomer to policy-making as the case, it argues the importance of conceptualizing the global/local dynamics in policy-making for assisted reproductive technology (ART). The conceptual framework is built upon recent literature on standardization, science policy, and global assemblage. I propose three interrelated features that reveal the "global in the local": (1) the power relationships among stakeholders, (2) the selected global form that involved actors drew upon, and (3) the re-contextualized assemblage made of local networks. Data included archives, interviews, and participant observation. In different historical periods the specific stakeholders selected different preferred global forms for Taiwan, such as Britain's code of ethics in the 1990s, the American guideline in the early 2000s, and the European trend in the mid-2000s. The global is heterogeneous. The failure to transfer the British regulation, the revision of the American guideline by adding one more embryo than it specified, and the gap between the cited European trend and the "no more than four" in Taiwan's 2007 Human Reproduction Law all show that the local network further transforms the selected global form, confining it to rhetoric only or tailoring it to local needs. Overall, Taiwanese practitioners successfully maintained their medical autonomy to build a 'flexible standardization'. Multiple pregnancy remains the most common health risk of IVF in Taiwan. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. Free Energy Reconstruction from Logarithmic Mean-Force Dynamics Using Multiple Nonequilibrium Trajectories.

    Science.gov (United States)

    Morishita, Tetsuya; Yonezawa, Yasushige; Ito, Atsushi M

    2017-07-11

    Efficient and reliable estimation of the mean force (MF), the derivatives of the free energy with respect to a set of collective variables (CVs), has been a challenging problem because free energy differences are often computed by integrating the MF. Among various methods for computing free energy differences, logarithmic mean-force dynamics (LogMFD) [ Morishita et al., Phys. Rev. E 2012 , 85 , 066702 ] invokes the conservation law in classical mechanics to integrate the MF, which allows us to estimate the free energy profile along the CVs on-the-fly. Here, we present a method called parallel dynamics, which improves the estimation of the MF by employing multiple replicas of the system and is straightforwardly incorporated in LogMFD or a related method. In the parallel dynamics, the MF is evaluated by a nonequilibrium path-ensemble using the multiple replicas based on the Crooks-Jarzynski nonequilibrium work relation. Thanks to the Crooks relation, realizing full-equilibrium states is no longer mandatory for estimating the MF. Additionally, sampling in the hidden subspace orthogonal to the CV space is highly improved with appropriate weights for each metastable state (if any), which is hardly achievable by typical free energy computational methods. We illustrate how to implement parallel dynamics by combining it with LogMFD, which we call logarithmic parallel dynamics (LogPD). Biosystems of alanine dipeptide and adenylate kinase in explicit water are employed as benchmark systems to which LogPD is applied to demonstrate the effect of multiple replicas on the accuracy and efficiency in estimating the free energy profiles using parallel dynamics.

  4. CO rebinding kinetics and molecular dynamics simulations highlight dynamic regulation of internal cavities in human cytoglobin.

    Directory of Open Access Journals (Sweden)

    Matteo Gabba

    Full Text Available Cytoglobin (Cygb was recently discovered in the human genome and localized in different tissues. It was suggested to play tissue-specific protective roles, spanning from scavenging of reactive oxygen species in neurons to supplying oxygen to enzymes in fibroblasts. To shed light on the functioning of such versatile machinery, we have studied the processes supporting transport of gaseous heme ligands in Cygb. Carbon monoxide rebinding shows a complex kinetic pattern with several distinct reaction intermediates, reflecting rebinding from temporary docking sites, second order recombination, and formation (and dissociation of a bis-histidyl heme hexacoordinated reaction intermediate. Ligand exit to the solvent occurs through distinct pathways, some of which exploit temporary docking sites. The remarkable change in energetic barriers, linked to heme bis-histidyl hexacoordination by HisE7, may be responsible for active regulation of the flux of reactants and products to and from the reaction site on the distal side of the heme. A substantial change in both protein dynamics and inner cavities is observed upon transition from the CO-liganded to the pentacoordinated and bis-histidyl hexacoordinated species, which could be exploited as a signalling state. These findings are consistent with the expected versatility of the molecular activity of this protein.

  5. Effect of Food Regulation on the Spanish Food Processing Industry: A Dynamic Productivity Analysis.

    Science.gov (United States)

    Kapelko, Magdalena; Oude Lansink, Alfons; Stefanou, Spiro E

    2015-01-01

    This article develops the decomposition of the dynamic Luenberger productivity growth indicator into dynamic technical change, dynamic technical inefficiency change and dynamic scale inefficiency change in the dynamic directional distance function context using Data Envelopment Analysis. These results are used to investigate for the Spanish food processing industry the extent to which dynamic productivity growth and its components are affected by the introduction of the General Food Law in 2002 (Regulation (EC) No 178/2002). The empirical application uses panel data of Spanish meat, dairy, and oils and fats industries over the period 1996-2011. The results suggest that in the oils and fats industry the impact of food regulation on dynamic productivity growth is negative initially and then positive over the long run. In contrast, the opposite pattern is observed for the meat and dairy processing industries. The results further imply that firms in the meat processing and oils and fats industries face similar impacts of food safety regulation on dynamic technical change, dynamic inefficiency change and dynamic scale inefficiency change.

  6. Effect of Food Regulation on the Spanish Food Processing Industry: A Dynamic Productivity Analysis

    Science.gov (United States)

    Kapelko, Magdalena; Lansink, Alfons Oude; Stefanou, Spiro E.

    2015-01-01

    This article develops the decomposition of the dynamic Luenberger productivity growth indicator into dynamic technical change, dynamic technical inefficiency change and dynamic scale inefficiency change in the dynamic directional distance function context using Data Envelopment Analysis. These results are used to investigate for the Spanish food processing industry the extent to which dynamic productivity growth and its components are affected by the introduction of the General Food Law in 2002 (Regulation (EC) No 178/2002). The empirical application uses panel data of Spanish meat, dairy, and oils and fats industries over the period 1996-2011. The results suggest that in the oils and fats industry the impact of food regulation on dynamic productivity growth is negative initially and then positive over the long run. In contrast, the opposite pattern is observed for the meat and dairy processing industries. The results further imply that firms in the meat processing and oils and fats industries face similar impacts of food safety regulation on dynamic technical change, dynamic inefficiency change and dynamic scale inefficiency change. PMID:26057878

  7. Effect of multiple resistive shells on the dynamics of the slinky mode in RFP plasmas

    Science.gov (United States)

    Guo, S. C.; Chu, M. S.

    2002-11-01

    The effects of multiple resistive shells and transient electromagnetic torque on the dynamics of mode locking in the RFP plasmas are studied. We study the EM torque acting on the tearing modes produced by a system of resistive shells. These shells may consist of several nested thin shells or several thin shells enclosed within a thick shell. Both the steady state theory and the time dependent theory are developed. The steady state theory is shown to provide accurate account of the resultant EM torque if (dω/dt)ω-2 slinky mode and its dynamics in the presence of resistive walls are discussed.

  8. DYNAMIC ANALYSIS OF A CRIMPING DEVICE WITH MULTIPLE CAMS USING MSC ADAMS II

    Directory of Open Access Journals (Sweden)

    Gheorghe Popescu

    2012-05-01

    Full Text Available Through the present paper, the author presents the results of the dynamic analysis with MSC ADAMS of the mechanism with a crimping device with 12 tightening cams, designed and used in the technological process of assembly of the indigenous electrical detonators. In this sense, the mechanism with multiple cams is considered a mechanical system and is treated as an assembly of rigid bodies connected by mechanical connections and elastic elements. For shaping and simulation of the mechanism with multiple cams using ADAMS program, the author got through the following stages: construction of the pattern, its testing and simulation, validation, finishing, parametrization, optimization of the pattern.

  9. Mechanisms regulating regional cerebral activation during dynamic handgrip in humans

    DEFF Research Database (Denmark)

    Williamson, James; Friedman, D B; Mitchell, J H

    1996-01-01

    Dynamic hand movement increases regional cerebral blood flow (rCBF) of the contralateral motor sensory cortex (MS1). This increase is eliminated by regional anesthesia of the working arm, indicating the importance of afferent neural input. The purpose of this study was to determine the specific...... type of afferent input required for this cerebral activation. The rCBF was measured at +5.0 and +9.0 cm above the orbitomeatal (OM) plane in 13 subjects during 1) rest; 2) dynamic left-hand contractions; 3) postcontraction ischemia (metaboreceptor afferents); and 4) biceps brachii tendon vibration...... (muscle spindles). The rCBF increased only during dynamic hand contraction; contralateral MS1 (OM +9) by 15% to 64 +/- 8.6 ml.100 g-1.min-1 (P

  10. Multiple spatially localized dynamical states in friction-excited oscillator chains

    Science.gov (United States)

    Papangelo, A.; Hoffmann, N.; Grolet, A.; Stender, M.; Ciavarella, M.

    2018-03-01

    Friction-induced vibrations are known to affect many engineering applications. Here, we study a chain of friction-excited oscillators with nearest neighbor elastic coupling. The excitation is provided by a moving belt which moves at a certain velocity vd while friction is modelled with an exponentially decaying friction law. It is shown that in a certain range of driving velocities, multiple stable spatially localized solutions exist whose dynamical behavior (i.e. regular or irregular) depends on the number of oscillators involved in the vibration. The classical non-repeatability of friction-induced vibration problems can be interpreted in light of those multiple stable dynamical states. These states are found within a "snaking-like" bifurcation pattern. Contrary to the classical Anderson localization phenomenon, here the underlying linear system is perfectly homogeneous and localization is solely triggered by the friction nonlinearity.

  11. ANGUSTIFOLIA mediates one of the multiple SCRAMBLED signaling pathways regulating cell growth pattern in Arabidopsis thaliana.

    Science.gov (United States)

    Kwak, Su-Hwan; Song, Sang-Kee; Lee, Myeong Min; Schiefelbein, John

    2015-09-25

    In Arabidopsis thaliana, an atypical leucine-rich repeat receptor-like kinase, SCRAMBLED (SCM), is required for multiple developmental processes including root epidermal cell fate determination, silique dehiscence, inflorescence growth, ovule morphogenesis, and tissue morphology. Previous work suggested that SCM regulates these multiple pathways using distinct mechanisms via interactions with specific downstream factors. ANGUSTIFOLIA (AN) is known to regulate cell and tissue morphogenesis by influencing cortical microtubule arrangement, and recently, the AN protein was reported to interact with the SCM protein. Therefore, we examined whether AN might be responsible for mediating some of the SCM-dependent phenotypes. We discovered that both scm and an mutant lines cause an abnormal spiral or twisting growth of roots, but only the scm mutant affected root epidermal patterning. The siliques of the an and scm mutants also exhibited spiral growth, as previously reported, but only the scm mutant altered silique dehiscence. Interestingly, we discovered that the spiral growth of roots and siliques of the scm mutant is rescued by a truncated SCM protein that lacks its kinase domain, and that a juxtamembrane domain of SCM was sufficient for AN binding in the yeast two-hybrid analysis. These results suggest that the AN protein is one of the critical downstream factors of SCM pathways specifically responsible for mediating its effects on cell/tissue morphogenesis through cortical microtubule arrangement. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Inhibition of Ubc13-mediated Ubiquitination by GPS2 Regulates Multiple Stages of B Cell Development.

    Science.gov (United States)

    Lentucci, Claudia; Belkina, Anna C; Cederquist, Carly T; Chan, Michelle; Johnson, Holly E; Prasad, Sherry; Lopacinski, Amanda; Nikolajczyk, Barbara S; Monti, Stefano; Snyder-Cappione, Jennifer; Tanasa, Bogdan; Cardamone, M Dafne; Perissi, Valentina

    2017-02-17

    Non-proteolytic ubiquitin signaling mediated by Lys 63 ubiquitin chains plays a critical role in multiple pathways that are key to the development and activation of immune cells. Our previous work indicates that GPS2 (G-protein Pathway Suppressor 2) is a multifunctional protein regulating TNFα signaling and lipid metabolism in the adipose tissue through modulation of Lys 63 ubiquitination events. However, the full extent of GPS2-mediated regulation of ubiquitination and the underlying molecular mechanisms are unknown. Here, we report that GPS2 is required for restricting the activation of TLR and BCR signaling pathways and the AKT/FOXO1 pathway in immune cells based on direct inhibition of Ubc13 enzymatic activity. Relevance of this regulatory strategy is confirmed in vivo by B cell-targeted deletion of GPS2, resulting in developmental defects at multiple stages of B cell differentiation. Together, these findings reveal that GPS2 genomic and non-genomic functions are critical for the development and cellular homeostasis of B cells. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. Differences in dynamic balance scores in one sport versus multiple sport high school athletes.

    Science.gov (United States)

    Gorman, Paul P; Butler, Robert J; Rauh, Mitchell J; Kiesel, Kyle; Plisky, Phillip J

    2012-04-01

    Researchers have previously reported on the importance of dynamic balance in assessing an individual's risk for injury during sport. However, to date there is no research on whether multiple sport participation affects dynamic balance ability. Therefore, the purpose of this study was to determine if there was a difference in dynamic balance scores in high school athletes that competed in one sport only as compared athletes who competed in multiple sports, as tested by the Lower Quarter Y Balance Test (YBT-LQ). Ninety-two high school athletes who participated in one sport were matched, by age, gender and sport played, to athletes who participated in the same sport as well as additional sports. All individuals were assessed using the YBT-LQ to examine differences in composite reach score and reach direction asymmetry between single sport and multiple sport athletes. The greatest reach distance of three trials in each reach direction for right and left lower-extremities was normalized by limb length and used for analysis. A two-way ANOVA (gender x number of sports played) was used to statistically analyze the variables in the study. No significant interactions or main effects related to number of sports played were observed for any YBT-LQ score (p>0.05). Male athletes exhibited significantly greater normalized reach values for the posteromedial, posterolateral, and composite reach while also exhibiting a larger anterior reach difference when compared to the females. Athletes who participated in multiple sports had similar performances on the YBT-LQ when compared to athletes who participated in a single sport. The findings of this study suggest that the number of sports played by a high school athlete does not need to be controlled for when evaluating dynamic balance with the YBT-LQ.

  14. Quantum theory of dynamic multiple light scattering in fluctuating disordered media

    International Nuclear Information System (INIS)

    Skipetrov, S. E.

    2007-01-01

    We formulate a quantum theory of dynamic multiple light scattering in fluctuating disordered media and calculate the fluctuation and the autocorrelation function of the photon number operator for light transmitted through a disordered slab. The effect of disorder on the information capacity of a quantum communication channel operating in a disordered environment is estimated, and the use of squeezed light in diffusing-wave spectroscopy is discussed

  15. Stress and serial adult metamorphosis: Multiple roles for the stress axis in socially regulated sex change

    Directory of Open Access Journals (Sweden)

    Tessa K Solomon-Lane

    2013-11-01

    Full Text Available Socially regulated sex change in teleost fishes is a striking example of social status information regulating biological function in the service of reproductive success. The establishment of social dominance in sex changing species is translated into a cascade of changes in behavior, physiology, neuroendocrine function, and morphology that transforms a female into a male, or vice versa. The hypothalamic-pituitary-interrenal axis (HPI, homologous to HP-adrenal axis in mammals and birds has been hypothesized to play a mechanistic role linking status to sex change. The HPA/I axis responds to environmental stressors by integrating relevant external and internal cues and coordinating biological responses including changes in behavior, energetics, physiology, and morphology (i.e., metamorphosis. Through actions of both corticotropin-releasing factor and glucocorticoids (GCs, the HPA/I axis has been implicated in processes central to sex change, including the regulation of agonistic behavior, social status, energetic investment, and life history transitions. In this paper, we review the hypothesized roles of the HPA/I axis in the regulation of sex change and how those hypotheses have been tested to date. We include original data on sex change in the bluebanded goby (Lythyrpnus dalli, a highly social fish capable of bidirectional sex change. We then propose a model for HPA/I involvement in sex change and discuss how these ideas might be tested in the future. Understanding the regulation of sex change has the potential to elucidate evolutionarily conserved mechanisms responsible for translating pertinent information about the environment into coordinated biological changes along multiple body axes.

  16. Confinement and dynamical regulation in two-dimensional convective turbulence

    DEFF Research Database (Denmark)

    Bian, N.H.; Garcia, O.E.

    2003-01-01

    In this work the nature of confinement improvement implied by the self-consistent generation of mean flows in two-dimensional convective turbulence is studied. The confinement variations are linked to two distinct regulation mechanisms which are also shown to be at the origin of low......-frequency bursting in the fluctuation level and the convective heat flux integral, both resulting in a state of large-scale intermittency. The first one involves the control of convective transport by sheared mean flows. This regulation relies on the conservative transfer of kinetic energy from tilted fluctuations...

  17. NKCC1 Regulates Migration Ability of Glioblastoma Cells by Modulation of Actin Dynamics and Interacting with Cofilin

    Directory of Open Access Journals (Sweden)

    Paula Schiapparelli

    2017-07-01

    Full Text Available Glioblastoma (GBM is the most aggressive primary brain tumor in adults. The mechanisms that confer GBM cells their invasive behavior are poorly understood. The electroneutral Na+-K+-2Cl− co-transporter 1 (NKCC1 is an important cell volume regulator that participates in cell migration. We have shown that inhibition of NKCC1 in GBM cells leads to decreased cell migration, in vitro and in vivo. We now report on the role of NKCC1 on cytoskeletal dynamics. We show that GBM cells display a significant decrease in F-actin content upon NKCC1 knockdown (NKCC1-KD. To determine the potential actin-regulatory mechanisms affected by NKCC1 inhibition, we studied NKCC1 protein interactions. We found that NKCC1 interacts with the actin-regulating protein Cofilin-1 and can regulate its membrane localization. Finally, we analyzed whether NKCC1 could regulate the activity of the small Rho-GTPases RhoA and Rac1. We observed that the active forms of RhoA and Rac1 were decreased in NKCC1-KD cells. In summary, we report that NKCC1 regulates GBM cell migration by modulating the cytoskeleton through multiple targets including F-actin regulation through Cofilin-1 and RhoGTPase activity. Due to its essential role in cell migration NKCC1 may serve as a specific therapeutic target to decrease cell invasion in patients with primary brain cancer.

  18. Regulation of hTERT by BCR-ABL at multiple levels in K562 cells

    International Nuclear Information System (INIS)

    Chai, Juin Hsien; Zhang, Yong; Tan, Wei Han; Chng, Wee Joo; Li, Baojie; Wang, Xueying

    2011-01-01

    The cytogenetic characteristic of Chronic Myeloid Leukemia (CML) is the formation of the Philadelphia chromosome gene product, BCR-ABL. Given that BCR-ABL is the specific target of Gleevec in CML treatment, we investigated the regulation of the catalytic component of telomerase, hTERT, by BCR-ABL at multiple levels in K562 cells. Molecular techniques such as over expression, knockdown, real-time PCR, immunoprecipitation, western blotting, reporter assay, confocal microscopy, telomerase assays and microarray were used to suggest that hTERT expression and activity is modulated by BCR-ABL at multiple levels. Our results suggest that BCR-ABL plays an important role in regulating hTERT in K562 (BCR-ABL positive human leukemia) cells. When Gleevec inhibited the tyrosine kinase activity of BCR-ABL, phosphorylation of hTERT was downregulated, therefore suggesting a positive correlation between BCR-ABL and hTERT. Gleevec treatment inhibited hTERT at mRNA level and significantly reduced telomerase activity (TA) in K562 cells, but not in HL60 or Jurkat cells (BCR-ABL negative cells). We also demonstrated that the transcription factor STAT5a plays a critical role in hTERT gene regulation in K562 cells. Knockdown of STAT5a, but not STAT5b, resulted in a marked downregulation of hTERT mRNA level, TA and hTERT protein level in K562 cells. Furthermore, translocation of hTERT from nucleoli to nucleoplasm was observed in K562 cells induced by Gleevec. Our data reveal that BCR-ABL can regulate TA at multiple levels, including transcription, post-translational level, and proper localization. Thus, suppression of cell growth and induction of apoptosis by Gleevec treatment may be partially due to TA inhibition. Additionally, we have identified STAT5a as critical mediator of the hTERT gene expression in BCR-ABL positive CML cells, suggesting that targeting STAT5a may be a promising therapeutic strategy for BCR-ABL positive CML patients

  19. Nuclear Dynamics of BRCA1-Dependent Transcription Regulation

    National Research Council Canada - National Science Library

    Sharp, Zelton D

    2005-01-01

    ...) Construction of fluorescent GAL4-DBD and ZBRK1 fusion protein has been achieved, and BRCA1 derivatives are in progress. When operational, this system will document real time nuclear dynamics of ZBRK1/BRCA1-dependent chromatin modification systems, as cells mount transcriptional responses to genotoxins.

  20. The machinery at endoplasmic reticulum-plasma membrane contact sites contributes to spatial regulation of multiple Legionella effector proteins.

    Directory of Open Access Journals (Sweden)

    Andree Hubber

    2014-07-01

    Full Text Available The Dot/Icm system of the intracellular pathogen Legionella pneumophila has the capacity to deliver over 270 effector proteins into host cells during infection. Important questions remain as to spatial and temporal mechanisms used to regulate such a large array of virulence determinants after they have been delivered into host cells. Here we investigated several L. pneumophila effector proteins that contain a conserved phosphatidylinositol-4-phosphate (PI4P-binding domain first described in the effector DrrA (SidM. This PI4P binding domain was essential for the localization of effectors to the early L. pneumophila-containing vacuole (LCV, and DrrA-mediated recruitment of Rab1 to the LCV required PI4P-binding activity. It was found that the host cell machinery that regulates sites of contact between the plasma membrane (PM and the endoplasmic reticulum (ER modulates PI4P dynamics on the LCV to control localization of these effectors. Specifically, phosphatidylinositol-4-kinase IIIα (PI4KIIIα was important for generating a PI4P signature that enabled L. pneumophila effectors to localize to the PM-derived vacuole, and the ER-associated phosphatase Sac1 was involved in metabolizing the PI4P on the vacuole to promote the dissociation of effectors. A defect in L. pneumophila replication in macrophages deficient in PI4KIIIα was observed, highlighting that a PM-derived PI4P signature is critical for biogenesis of a vacuole that supports intracellular multiplication of L. pneumophila. These data indicate that PI4P metabolism by enzymes controlling PM-ER contact sites regulate the association of L. pneumophila effectors to coordinate early stages of vacuole biogenesis.

  1. Coupling dynamic analysis of spacecraft with multiple cylindrical tanks and flexible appendages

    Science.gov (United States)

    Wu, Wen-Jun; Yue, Bao-Zeng; Huang, Hua

    2016-02-01

    This paper is mainly concerned with the coupling dynamic analysis of a complex spacecraft consisting of one main rigid platform, multiple liquid-filled cylindrical tanks, and a number of flexible appendages. Firstly, the carrier potential function equations of liquid in the tanks are deduced according to the wall boundary conditions. Through employing the Fourier-Bessel series expansion method, the dynamic boundaries conditions on a curved free-surface under a low-gravity environment are transformed to general simple differential equations and the rigid-liquid coupled sloshing dynamic state equations of liquid in tanks are obtained. The state vectors of rigid-liquid coupled equations are composed with the modal coordinates of the relative potential function and the modal coordinates of wave height. Based on the Bernoulli-Euler beam theory and the D'Alembert's principle, the rigid-flexible coupled dynamic state equations of flexible appendages are directly derived, and the coordinate transform matrixes of maneuvering flexible appendages are precisely computed as time-varying. Then, the coupling dynamics state equations of the overall system of the spacecraft are modularly built by means of the Lagrange's equations in terms of quasi-coordinates. Lastly, the coupling dynamic performances of a typical complex spacecraft are studied. The availability and reliability of the presented method are also confirmed.

  2. A precisely regulated gene expression cassette potently modulates metastasis and survival in multiple solid cancers.

    Directory of Open Access Journals (Sweden)

    Kun Yu

    2008-07-01

    Full Text Available Successful tumor development and progression involves the complex interplay of both pro- and anti-oncogenic signaling pathways. Genetic components balancing these opposing activities are likely to require tight regulation, because even subtle alterations in their expression may disrupt this balance with major consequences for various cancer-associated phenotypes. Here, we describe a cassette of cancer-specific genes exhibiting precise transcriptional control in solid tumors. Mining a database of tumor gene expression profiles from six different tissues, we identified 48 genes exhibiting highly restricted levels of gene expression variation in tumors (n = 270 compared to nonmalignant tissues (n = 71. Comprising genes linked to multiple cancer-related pathways, the restricted expression of this "Poised Gene Cassette" (PGC was robustly validated across 11 independent cohorts of approximately 1,300 samples from multiple cancer types. In three separate experimental models, subtle alterations in PGC expression were consistently associated with significant differences in metastatic and invasive potential. We functionally confirmed this association in siRNA knockdown experiments of five PGC genes (p53CSV, MAP3K11, MTCH2, CPSF6, and SKIP, which either directly enhanced the invasive capacities or inhibited the proliferation of AGS cancer cells. In primary tumors, similar subtle alterations in PGC expression were also repeatedly associated with clinical outcome in multiple cohorts. Taken collectively, these findings support the existence of a common set of precisely controlled genes in solid tumors. Since inducing small activity changes in these genes may prove sufficient to potently influence various tumor phenotypes such as metastasis, targeting such precisely regulated genes may represent a promising avenue for novel anti-cancer therapies.

  3. C/EBPβ Mediates Growth Hormone-Regulated Expression of Multiple Target Genes

    Science.gov (United States)

    Cui, Tracy X.; Lin, Grace; LaPensee, Christopher R.; Calinescu, Anda-Alexandra; Rathore, Maanjot; Streeter, Cale; Piwien-Pilipuk, Graciela; Lanning, Nathan; Jin, Hui; Carter-Su, Christin; Qin, Zhaohui S.

    2011-01-01

    Regulation of c-Fos transcription by GH is mediated by CCAAT/enhancer binding protein β (C/EBPβ). This study examines the role of C/EBPβ in mediating GH activation of other early response genes, including Cyr61, Btg2, Socs3, Zfp36, and Socs1. C/EBPβ depletion using short hairpin RNA impaired responsiveness of these genes to GH, as seen for c-Fos. Rescue with wild-type C/EBPβ led to GH-dependent recruitment of the coactivator p300 to the c-Fos promoter. In contrast, rescue with C/EBPβ mutated at the ERK phosphorylation site at T188 failed to induce GH-dependent recruitment of p300, indicating that ERK-mediated phosphorylation of C/EBPβ at T188 is required for GH-induced recruitment of p300 to c-Fos. GH also induced the occupancy of phosphorylated C/EBPβ and p300 on Cyr61, Btg2, and Socs3 at predicted C/EBP-cAMP response element-binding protein motifs in their promoters. Consistent with a role for ERKs in GH-induced expression of these genes, treatment with U0126 to block ERK phosphorylation inhibited their GH-induced expression. In contrast, GH-dependent expression of Zfp36 and Socs1 was not inhibited by U0126. Thus, induction of multiple early response genes by GH in 3T3-F442A cells is mediated by C/EBPβ. A subset of these genes is regulated similarly to c-Fos, through a mechanism involving GH-stimulated ERK 1/2 activation, phosphorylation of C/EBPβ, and recruitment of p300. Overall, these studies suggest that C/EBPβ, like the signal transducer and activator of transcription proteins, regulates multiple genes in response to GH. PMID:21292824

  4. The Dynamics and Sliding Mode Control of Multiple Cooperative Welding Robot Manipulators

    Directory of Open Access Journals (Sweden)

    Bin Zi

    2012-08-01

    Full Text Available This paper deals with the design, dynamic modelling and sliding mode control of multiple cooperative welding robot manipulators (MWRMs. The MWRMs can handle complex tasks that are difficult or even impossible for a single manipulator. The kinematics and dynamics of the MWRMs are studied on the basis of the Denavit-Hartenberg and Lagrange method. Following that, considering the MWRM system with nonlinear and unknown disturbances, a non-singular terminal sliding mode control strategy is designed. By means of the Lyapunov function, the stability of the controller is proved. Simulation results indicate that the good control performance of the MWRMs is achieved by the non-singular terminal sliding mode controller, which also illustrates the correctness of the dynamic modelling and effectiveness of the proposed control strategy.

  5. Symbolic dynamics and synchronization of coupled map networks with multiple delays

    International Nuclear Information System (INIS)

    Atay, Fatihcan M.; Jalan, Sarika; Jost, Juergen

    2010-01-01

    We use symbolic dynamics to study discrete-time dynamical systems with multiple time delays. We exploit the concept of avoiding sets, which arise from specific non-generating partitions of the phase space and restrict the occurrence of certain symbol sequences related to the characteristics of the dynamics. In particular, we show that the resulting forbidden sequences are closely related to the time delays in the system. We present two applications to coupled map lattices, namely (1) detecting synchronization and (2) determining unknown values of the transmission delays in networks with possibly directed and weighted connections and measurement noise. The method is applicable to multi-dimensional as well as set-valued maps, and to networks with time-varying delays and connection structure.

  6. Correlation Coefficient between Dynamic Single Valued Neutrosophic Multisets and Its Multiple Attribute Decision-Making Method

    Directory of Open Access Journals (Sweden)

    Jun Ye

    2017-04-01

    Full Text Available Based on dynamic information collected from different time intervals in some real situations, this paper firstly proposes a dynamic single valued neutrosophic multiset (DSVNM to express dynamic information and operational relations of DSVNMs. Then, a correlation coefficient between DSVNMs and a weighted correlation coefficient between DSVNMs are presented to measure the correlation degrees between DSVNMs, and their properties are investigated. Based on the weighted correlation coefficient of DSVNMs, a multiple attribute decision-making method is established under a DSVNM environment, in which the evaluation values of alternatives with respect to attributes are collected from different time intervals and are represented by the form of DSVNMs. The ranking order of alternatives is performed through the weighted correlation coefficient between an alternative and the ideal alternative, which is considered by the attribute weights and the time weights, and thus the best one(s can also be determined. Finally, a practical example shows the application of the proposed method.

  7. Multiple bunch longitudinal dynamics measurements at the Cornell Electron-Positron Storage Ring

    Directory of Open Access Journals (Sweden)

    R. Holtzapple

    2001-01-01

    Full Text Available The Cornell Electron-Positron Storage Ring (CESR has a longitudinal dipole-coupled-bunch instability that limits the total amount of current that can be stored in the ring without feedback. As a result, it is one of the major limitations for higher stored current and luminosity. This paper reports the measurements of multiple bunch longitudinal dynamics done on CESR with a streak camera. The camera was used to measure the dependence of the bunch distribution on current and accelerating rf voltage, for multiple bunches stored in CESR, as well as the effects of the longitudinal instability on the bunch distribution. Measurements of the beam's longitudinal bunch distribution with multiple bunches present in the ring help give an understanding of the instability, how it affects the bunch distribution, and possibly give insight into a cure of the instability.

  8. A new multiple robot path planning algorithm: dynamic distributed particle swarm optimization.

    Science.gov (United States)

    Ayari, Asma; Bouamama, Sadok

    2017-01-01

    Multiple robot systems have become a major study concern in the field of robotic research. Their control becomes unreliable and even infeasible if the number of robots increases. In this paper, a new dynamic distributed particle swarm optimization (D 2 PSO) algorithm is proposed for trajectory path planning of multiple robots in order to find collision-free optimal path for each robot in the environment. The proposed approach consists in calculating two local optima detectors, LOD pBest and LOD gBest . Particles which are unable to improve their personal best and global best for predefined number of successive iterations would be replaced with restructured ones. Stagnation and local optima problems would be avoided by adding diversity to the population, without losing the fast convergence characteristic of PSO. Experiments with multiple robots are provided and proved effectiveness of such approach compared with the distributed PSO.

  9. No evidence of volatile chemicals regulating reproduction in a multiple queen ant

    Science.gov (United States)

    Coston, Duncan J.; Gill, Richard J.; Hammond, Robert L.

    2011-07-01

    Efficient cooperation in eusocial insect colonies requires effective communication, and there is abundant evidence of non-volatile chemicals playing a role in regulating reproduction within colonies. In contrast, there have been fewer studies investigating the role of volatile chemicals. This study investigated the potential role of volatile chemicals in regulating queen reproduction either by directly inhibiting queen reproduction or by honestly signalling queen fecundity to workers. We tested this using multiple queen colonies of the ant ( Leptothorax acervorum) from a functionally monogynous population where one queen monopolizes all reproduction. Nine colonies, each with an established laying queen, were split to produce two colony fragments—one containing the reproducing queen (group 1) and one containing only previously non-reproducing queens (group 2). Each group was separated by a fine wire mesh preventing physical contact, but allowing volatile chemical contact. In each group 2 fragment, we found that a single formerly non-reproductive queen commenced reproduction and that the rate of egg laying and maximum number of eggs recorded did not significantly differ between groups 1 and 2, results that do not support volatile chemicals as playing a role in regulating queen reproduction. Instead, our findings suggest that physical contact is necessary to maintain functional monogyny.

  10. Chromatin interaction of TATA-binding protein is dynamically regulated in human cells.

    Science.gov (United States)

    de Graaf, Petra; Mousson, Florence; Geverts, Bart; Scheer, Elisabeth; Tora, Laszlo; Houtsmuller, Adriaan B; Timmers, H Th Marc

    2010-08-01

    Gene transcription in mammalian cells is a dynamic process involving regulated assembly of transcription complexes on chromatin in which the TATA-binding protein (TBP) plays a central role. Here, we investigate the dynamic behaviour of TBP by a combination of fluorescence recovery after photobleaching (FRAP) and biochemical assays using human cell lines of different origin. The majority of nucleoplasmic TBP and other TFIID subunits associate with chromatin in a highly dynamic manner. TBP dynamics are regulated by the joint action of the SNF2-related BTAF1 protein and the NC2 complex. Strikingly, both BTAF1 and NC2 predominantly affect TBP dissociation rates, leaving the association rate unchanged. Chromatin immunoprecipitation shows that BTAF1 negatively regulates TBP and NC2 binding to active promoters. Our results support a model for a BTAF1-mediated release of TBP-NC2 complexes from chromatin.

  11. Dynamic Spectrum Access: regulations, standards and green radio policy considerations

    CSIR Research Space (South Africa)

    Mfupe, L

    2012-09-01

    Full Text Available -related requirements of electric utilities so that FCC can advise appropriately on federal smart grid policies and governmental departments on improving the energy-efficiency of their data centres [20]. Table 1 presents a SWOT analysis on green radio policies. IV... Table 1: A summary SWOT analysis of green radio policies. Method vs. Indicator Strengths Weaknesses Opportunities Threats Green radio compliance strategies ? Some regulators, telecommunications operators and standardization bodies around...

  12. Dynamic Nature of Noncoding RNA Regulation of Adaptive Immune Response

    Directory of Open Access Journals (Sweden)

    Franca Citarella

    2013-08-01

    Full Text Available Immune response plays a fundamental role in protecting the organism from infections; however, dysregulation often occurs and can be detrimental for the organism, leading to a variety of immune-mediated diseases. Recently our understanding of the molecular and cellular networks regulating the immune response, and, in particular, adaptive immunity, has improved dramatically. For many years, much of the focus has been on the study of protein regulators; nevertheless, recent evidence points to a fundamental role for specific classes of noncoding RNAs (ncRNAs in regulating development, activation and homeostasis of the immune system. Although microRNAs (miRNAs are the most comprehensive and well-studied, a number of reports suggest the exciting possibility that long ncRNAs (lncRNAs could mediate host response and immune function. Finally, evidence is also accumulating that suggests a role for miRNAs and other small ncRNAs in autocrine, paracrine and exocrine signaling events, thus highlighting an elaborate network of regulatory interactions mediated by different classes of ncRNAs during immune response. This review will explore the multifaceted roles of ncRNAs in the adaptive immune response. In particular, we will focus on the well-established role of miRNAs and on the emerging role of lncRNAs and circulating ncRNAs, which all make indispensable contributions to the understanding of the multilayered modulation of the adaptive immune response.

  13. Epithelial SCAP/INSIG/SREBP signaling regulates multiple biological processes during perinatal lung maturation.

    Directory of Open Access Journals (Sweden)

    James P Bridges

    Full Text Available Pulmonary surfactant is required for lung function at birth and throughout postnatal life. Defects in the surfactant system are associated with common pulmonary disorders including neonatal respiratory distress syndrome and acute respiratory distress syndrome in children and adults. Lipogenesis is essential for the synthesis of pulmonary surfactant by type II epithelial cells lining the alveoli. This study sought to identify the role of pulmonary epithelial SREBP, a transcriptional regulator of cellular lipid homeostasis, during a critical time period of perinatal lung maturation in the mouse. Genome wide mRNA expression profiling of lung tissue from transgenic mice with epithelial-specific deletions of Scap (Scap(Δ/Δ, resulting in inactivation of SREBP signaling or Insig1 and Insig2 (Insig1/2(Δ/Δ, resulting in activation of SREBP signaling was assessed. Differentially expressed genes responding to SREBP perturbations were identified and subjected to functional enrichment analysis, pathway mapping and literature mining to predict upstream regulators and transcriptional networks regulating surfactant lipid homeostasis. Through comprehensive data analysis and integration, time dependent effects of epithelial SCAP/INSIG/SREBP deletion and defined SCAP/INSIG/SREBP-associated genes, bioprocesses and downstream pathways were identified. SREBP signaling influences epithelial development, cell death and cell proliferation at E17.5, while primarily influencing surfactant physiology, lipid/sterol synthesis, and phospholipid transport after birth. SREBP signaling integrated with the Wnt/β-catenin and glucocorticoid receptor signaling pathways during perinatal lung maturation. SREBP regulates perinatal lung lipogenesis and maturation through multiple mechanisms by interactions with distinct sets of regulatory partners.

  14. Epithelial SCAP/INSIG/SREBP signaling regulates multiple biological processes during perinatal lung maturation.

    Science.gov (United States)

    Bridges, James P; Schehr, Angelica; Wang, Yanhua; Huo, Liya; Besnard, Valérie; Ikegami, Machiko; Whitsett, Jeffrey A; Xu, Yan

    2014-01-01

    Pulmonary surfactant is required for lung function at birth and throughout postnatal life. Defects in the surfactant system are associated with common pulmonary disorders including neonatal respiratory distress syndrome and acute respiratory distress syndrome in children and adults. Lipogenesis is essential for the synthesis of pulmonary surfactant by type II epithelial cells lining the alveoli. This study sought to identify the role of pulmonary epithelial SREBP, a transcriptional regulator of cellular lipid homeostasis, during a critical time period of perinatal lung maturation in the mouse. Genome wide mRNA expression profiling of lung tissue from transgenic mice with epithelial-specific deletions of Scap (Scap(Δ/Δ), resulting in inactivation of SREBP signaling) or Insig1 and Insig2 (Insig1/2(Δ/Δ), resulting in activation of SREBP signaling) was assessed. Differentially expressed genes responding to SREBP perturbations were identified and subjected to functional enrichment analysis, pathway mapping and literature mining to predict upstream regulators and transcriptional networks regulating surfactant lipid homeostasis. Through comprehensive data analysis and integration, time dependent effects of epithelial SCAP/INSIG/SREBP deletion and defined SCAP/INSIG/SREBP-associated genes, bioprocesses and downstream pathways were identified. SREBP signaling influences epithelial development, cell death and cell proliferation at E17.5, while primarily influencing surfactant physiology, lipid/sterol synthesis, and phospholipid transport after birth. SREBP signaling integrated with the Wnt/β-catenin and glucocorticoid receptor signaling pathways during perinatal lung maturation. SREBP regulates perinatal lung lipogenesis and maturation through multiple mechanisms by interactions with distinct sets of regulatory partners.

  15. Analysis of Dynamic Performance of a Kalman Filter for Combining Multiple MEMS Gyroscopes

    Directory of Open Access Journals (Sweden)

    Liang Xue

    2014-11-01

    Full Text Available In this paper, the dynamic performance of a Kalman filter (KF was analyzed, which is used to combine multiple measurements of a gyroscopes array to reduce the noise and improve the accuracy of the individual sensors. A principle for accuracy improvement by the KF was briefly presented to obtain an optimal estimate of input rate signal. In particular, the influences of some crucial factors on the KF dynamic performance were analyzed by simulations such as the factors input signal frequency, signal sampling, and KF filtering rate. Finally, a system that was comprised of a six-gyroscope array was designed and implemented to test the dynamic performance. Experimental results indicated that the 1σ error for the combined rate signal was reduced to about 0.2°/s in the constant rate test, which was a reduction by a factor of more than eight compared to the single gyroscope. The 1σ error was also reduced from 1.6°/s to 0.48°/s in the swing test. It showed that the estimated angular rate signal could well reflect the dynamic characteristic of the input signal in dynamic conditions.

  16. Multiple-Trapping Model for the Charge Recombination Dynamics in Mesoporous-Structured Perovskite Solar Cells.

    Science.gov (United States)

    Wang, Hao-Yi; Wang, Yi; Hao, Ming-Yang; Qin, Yujun; Fu, Li-Min; Guo, Zhi-Xin; Ai, Xi-Cheng; Zhang, Jian-Ping

    2017-12-22

    The photovoltaic performance of organic-inorganic hybrid perovskite solar cells has reached a bottleneck after rapid development in last few years. Further breakthrough in this field requires deeper understanding of the underlying mechanism of the photoelectric conversion process in the device, especially the dynamics of charge-carrier recombination. Originating from dye-sensitized solar cells (DSSCs), mesoporous-structured perovskite solar cells (MPSCs) have shown many similarities to DSSCs with respect to their photoelectric dynamics. Herein, by applying the multiple-trapping model of the charge-recombination dynamic process for DSSCs in MPSCs, with rational modification, a novel physical model is proposed to describe the dynamics of charge recombination in MPSCs that exhibits good agreement with experimental data. Accordingly, the perovskite- and TiO 2 -dominating charge-recombination processes are assigned and their relationships with the trap-state distribution are also discussed. An optimal balance between these two dynamic processes is required to improve the performance of mesoporous-structured perovskite devices. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. High Dynamic Velocity Range Particle Image Velocimetry Using Multiple Pulse Separation Imaging

    Directory of Open Access Journals (Sweden)

    Tadhg S. O’Donovan

    2010-12-01

    Full Text Available The dynamic velocity range of particle image velocimetry (PIV is determined by the maximum and minimum resolvable particle displacement. Various techniques have extended the dynamic range, however flows with a wide velocity range (e.g., impinging jets still challenge PIV algorithms. A new technique is presented to increase the dynamic velocity range by over an order of magnitude. The multiple pulse separation (MPS technique (i records series of double-frame exposures with different pulse separations, (ii processes the fields using conventional multi-grid algorithms, and (iii yields a composite velocity field with a locally optimized pulse separation. A robust criterion determines the local optimum pulse separation, accounting for correlation strength and measurement uncertainty. Validation experiments are performed in an impinging jet flow, using laser-Doppler velocimetry as reference measurement. The precision of mean flow and turbulence quantities is significantly improved compared to conventional PIV, due to the increase in dynamic range. In a wide range of applications, MPS PIV is a robust approach to increase the dynamic velocity range without restricting the vector evaluation methods.

  18. High dynamic velocity range particle image velocimetry using multiple pulse separation imaging.

    Science.gov (United States)

    Persoons, Tim; O'Donovan, Tadhg S

    2011-01-01

    The dynamic velocity range of particle image velocimetry (PIV) is determined by the maximum and minimum resolvable particle displacement. Various techniques have extended the dynamic range, however flows with a wide velocity range (e.g., impinging jets) still challenge PIV algorithms. A new technique is presented to increase the dynamic velocity range by over an order of magnitude. The multiple pulse separation (MPS) technique (i) records series of double-frame exposures with different pulse separations, (ii) processes the fields using conventional multi-grid algorithms, and (iii) yields a composite velocity field with a locally optimized pulse separation. A robust criterion determines the local optimum pulse separation, accounting for correlation strength and measurement uncertainty. Validation experiments are performed in an impinging jet flow, using laser-Doppler velocimetry as reference measurement. The precision of mean flow and turbulence quantities is significantly improved compared to conventional PIV, due to the increase in dynamic range. In a wide range of applications, MPS PIV is a robust approach to increase the dynamic velocity range without restricting the vector evaluation methods.

  19. Catecholaminergic Regulation of Learning Rate in a Dynamic Environment

    Science.gov (United States)

    Jepma, Marieke; Nassar, Matthew R.; Rangel-Gomez, Mauricio; Meeter, Martijn; Nieuwenhuis, Sander

    2016-01-01

    Adaptive behavior in a changing world requires flexibly adapting one’s rate of learning to the rate of environmental change. Recent studies have examined the computational mechanisms by which various environmental factors determine the impact of new outcomes on existing beliefs (i.e., the ‘learning rate’). However, the brain mechanisms, and in particular the neuromodulators, involved in this process are still largely unknown. The brain-wide neurophysiological effects of the catecholamines norepinephrine and dopamine on stimulus-evoked cortical responses suggest that the catecholamine systems are well positioned to regulate learning about environmental change, but more direct evidence for a role of this system is scant. Here, we report evidence from a study employing pharmacology, scalp electrophysiology and computational modeling (N = 32) that suggests an important role for catecholamines in learning rate regulation. We found that the P3 component of the EEG—an electrophysiological index of outcome-evoked phasic catecholamine release in the cortex—predicted learning rate, and formally mediated the effect of prediction-error magnitude on learning rate. P3 amplitude also mediated the effects of two computational variables—capturing the unexpectedness of an outcome and the uncertainty of a preexisting belief—on learning rate. Furthermore, a pharmacological manipulation of catecholamine activity affected learning rate following unanticipated task changes, in a way that depended on participants’ baseline learning rate. Our findings provide converging evidence for a causal role of the human catecholamine systems in learning-rate regulation as a function of environmental change. PMID:27792728

  20. Dynamic model of gene regulation for the lac operon

    Science.gov (United States)

    Angelova, Maia; Ben-Halim, Asma

    2011-03-01

    Gene regulatory network is a collection of DNA which interact with each other and with other matter in the cell. The lac operon is an example of a relatively simple genetic network and is one of the best-studied structures in the Escherichia coli bacteria. In this work we consider a deterministic model of the lac operon with a noise term, representing the stochastic nature of the regulation. The model is written in terms of a system of simultaneous first order differential equations with delays. We investigate an analytical and numerical solution and analyse the range of values for the parameters corresponding to a stable solution.

  1. Dynamic model of gene regulation for the lac operon

    International Nuclear Information System (INIS)

    Angelova, Maia; Ben-Halim, Asma

    2011-01-01

    Gene regulatory network is a collection of DNA which interact with each other and with other matter in the cell. The lac operon is an example of a relatively simple genetic network and is one of the best-studied structures in the Escherichia coli bacteria. In this work we consider a deterministic model of the lac operon with a noise term, representing the stochastic nature of the regulation. The model is written in terms of a system of simultaneous first order differential equations with delays. We investigate an analytical and numerical solution and analyse the range of values for the parameters corresponding to a stable solution.

  2. ALKBH4-dependent demethylation of actin regulates actomyosin dynamics

    DEFF Research Database (Denmark)

    Li, M.-M.; Shi, Y.; Niu, Y.

    2013-01-01

    -type but not catalytically inactive ALKBH4. Similar to actin and myosin knock-out mice, homozygous Alkbh4 mutant mice display early embryonic lethality. These findings imply that ALKBH4-dependent actin demethylation regulates actomyosin function by promoting actin-non-muscle myosin II interaction.......-dependent processes such as cytokinesis and cell migration. ALKBH4-deficient cells display elevated K84me1 levels. Non-muscle myosin II only interacts with unmethylated actin and its proper recruitment to and interaction with actin depend on ALKBH4. ALKBH4 co-localizes with the actomyosin-based contractile ring...

  3. Dynamical Processes in Ageing, Gene Regulation and Communication

    DEFF Research Database (Denmark)

    Bendtsen, Kristian Moss

    project we constructed a mathematical model and showed that if DNA damage is primarily caused by geno-toxic agents, it would be advantageous for cells to have a fragile DNA repair mechanism. The second part of my Ph.D. thesis covers gene regulation. In the first project we show how RNA polymerase can...... is that unstable activation and stable repression is a requirement for the motif to produce oscillations. The last part of this thesis studies the emergence of communication networks. In this study we constructed a simple e-mail game. E-mails from two session with 16 players, who had never met before, showed how...

  4. Dynamical Processes in Ageing, Gene Regulation and Communication

    DEFF Research Database (Denmark)

    Bendtsen, Kristian Moss

    My thesis consists of three parts. The first part covers ageing phenomena. In the first project I measured the mobility of two DNA repair proteins. Contrasting diffusion coefficients from literature I was able to classify DNA repair protein into either "scanners" or "responders". In a second...... project we constructed a mathematical model and showed that if DNA damage is primarily caused by geno-toxic agents, it would be advantageous for cells to have a fragile DNA repair mechanism. The second part of my Ph.D. thesis covers gene regulation. In the first project we show how RNA polymerase can...

  5. Baroreflex regulation of blood pressure during dynamic exercise

    Science.gov (United States)

    Raven, P. B.; Potts, J. T.; Shi, X.; Blomqvist, C. G. (Principal Investigator)

    1997-01-01

    From the work of Potts et al. Papelier et al. and Shi et al. it is readily apparent that the arterial (aortic and carotid) baroreflexes are reset to function at the prevailing ABP of exercise. The blood pressure of exercise is the result of the hemodynamic (cardiac output and TPR) responses, which appear to be regulated by two redundant neural control systems, "Central Command" and the "exercise pressor reflex". Central Command is a feed-forward neural control system that operates in parallel with the neural regulation of the locomotor system and appears to establish the hemodynamic response to exercise. Within the central nervous system it appears that the HLR may be the operational site for Central Command. Specific neural sites within the HLR have been demonstrated in animals to be active during exercise. With the advent of positron emission tomography (PET) and single-photon emission computed tomography (SPECT), the anatomical areas of the human brain related to Central Command are being mapped. It also appears that the Nucleus Tractus Solitarius and the ventrolateral medulla may serve as an integrating site as they receive neural information from the working muscles via the group III/IV muscle afferents as well as from higher brain centers. This anatomical site within the CNS is now the focus of many investigations in which arterial baroreflex function, Central Command and the "exercise pressor reflex" appear to demonstrate inhibitory or facilitatory interaction. The concept of whether Central Command is the prime mover in the resetting of the arterial baroreceptors to function at the exercising ABP or whether the resetting is an integration of the "exercise pressor reflex" information with that of Central Command is now under intense investigation. However, it would be justified to conclude, from the data of Bevegard and Shepherd, Dicarlo and Bishop, Potts et al., and Papelier et al. that the act of exercise results in the resetting of the arterial baroreflex

  6. Multiple Time-Step Dual-Hamiltonian Hybrid Molecular Dynamics - Monte Carlo Canonical Propagation Algorithm.

    Science.gov (United States)

    Chen, Yunjie; Kale, Seyit; Weare, Jonathan; Dinner, Aaron R; Roux, Benoît

    2016-04-12

    A multiple time-step integrator based on a dual Hamiltonian and a hybrid method combining molecular dynamics (MD) and Monte Carlo (MC) is proposed to sample systems in the canonical ensemble. The Dual Hamiltonian Multiple Time-Step (DHMTS) algorithm is based on two similar Hamiltonians: a computationally expensive one that serves as a reference and a computationally inexpensive one to which the workload is shifted. The central assumption is that the difference between the two Hamiltonians is slowly varying. Earlier work has shown that such dual Hamiltonian multiple time-step schemes effectively precondition nonlinear differential equations for dynamics by reformulating them into a recursive root finding problem that can be solved by propagating a correction term through an internal loop, analogous to RESPA. Of special interest in the present context, a hybrid MD-MC version of the DHMTS algorithm is introduced to enforce detailed balance via a Metropolis acceptance criterion and ensure consistency with the Boltzmann distribution. The Metropolis criterion suppresses the discretization errors normally associated with the propagation according to the computationally inexpensive Hamiltonian, treating the discretization error as an external work. Illustrative tests are carried out to demonstrate the effectiveness of the method.

  7. Modeling Intraindividual Dynamics Using Stochastic Differential Equations: Age Differences in Affect Regulation.

    Science.gov (United States)

    Wood, Julie; Oravecz, Zita; Vogel, Nina; Benson, Lizbeth; Chow, Sy-Miin; Cole, Pamela; Conroy, David E; Pincus, Aaron L; Ram, Nilam

    2017-12-15

    Life-span theories of aging suggest improvements and decrements in individuals' ability to regulate affect. Dynamic process models, with intensive longitudinal data, provide new opportunities to articulate specific theories about individual differences in intraindividual dynamics. This paper illustrates a method for operationalizing affect dynamics using a multilevel stochastic differential equation (SDE) model, and examines how those dynamics differ with age and trait-level tendencies to deploy emotion regulation strategies (reappraisal and suppression). Univariate multilevel SDE models, estimated in a Bayesian framework, were fit to 21 days of ecological momentary assessments of affect valence and arousal (average 6.93/day, SD = 1.89) obtained from 150 adults (age 18-89 years)-specifically capturing temporal dynamics of individuals' core affect in terms of attractor point, reactivity to biopsychosocial (BPS) inputs, and attractor strength. Older age was associated with higher arousal attractor point and less BPS-related reactivity. Greater use of reappraisal was associated with lower valence attractor point. Intraindividual variability in regulation strategy use was associated with greater BPS-related reactivity and attractor strength, but in different ways for valence and arousal. The results highlight the utility of SDE models for studying affect dynamics and informing theoretical predictions about how intraindividual dynamics change over the life course. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  8. Dynamic control of biped locomotion robot using optimal regulator

    Energy Technology Data Exchange (ETDEWEB)

    Sano, Akihito; Furusho, Junji

    1988-08-01

    For moving in indoor space, it is generally recognized that biped locomotion is suitable. This paper proposes a hierarchical control strategy for the lower level where the position control or the force control at each joint is implemented. In the upper level control, the robot motion is divided into a sagittal plane and a lateral plane. We applied the optimal control algorithm to the motion control in the lateral plane in order to improve the robustness of the control system. The effects of these control schemes are shown by the experiments using the new walking robot BLR-G 1 and the parallel calculation system. BLR-G 1 has 9 degrees of freedom and equips the foot-pressure-sensors and a rate gyroscope. Complete dynamic walking is realized, in which the cycle for each step is about 1.0 second.

  9. Dynamic regulation of cerebral DNA repair genes by psychological stress

    DEFF Research Database (Denmark)

    Forsberg, Kristin; Aalling, Nadia; Wörtwein, Gitta

    2015-01-01

    for maintaining genomic integrity. The aim of the present study was to characterize the pattern of cerebral DNA repair enzyme regulation after stress through the quantification of a targeted range of gene products involved in different types of DNA repair. 72 male Sprague-Dawley rats were subjected to either......Neuronal genotoxic insults from oxidative stress constitute a putative molecular link between stress and depression on the one hand, and cognitive dysfunction and dementia risk on the other. Oxidative modifications to DNA are repaired by specific enzymes; a process that plays a critical role...... restraint stress (6h/day) or daily handling (controls), and sacrificed after 1, 7 or 21 stress sessions. The mRNA expression of seven genes (Ogg1, Ape1, Ung1, Neil1, Xrcc1, Ercc1, Nudt1) involved in the repair of oxidatively damaged DNA was determined by quantitative real time polymerase chain reaction...

  10. Comparing and combining implicit ligand sampling with multiple steered molecular dynamics to study ligand migration processes in heme proteins.

    Science.gov (United States)

    Forti, Flavio; Boechi, Leonardo; Estrin, Dario A; Marti, Marcelo A

    2011-07-30

    The ubiquitous heme proteins perform a wide variety of tasks that rely on the subtle regulation of their affinity for small ligands like O2, CO, and NO. Ligand affinity is characterized by kinetic association and dissociation rate constants, that partially depend on ligand migration between the solvent and active site, mediated by the presence of internal cavities or tunnels. Different computational methods have been developed to study these processes which can be roughly divided in two strategies: those costly methods in which the ligand is treated explicitly during the simulations, and the free energy landscape of the process is computed; and those faster methods that use prior computed Molecular Dynamics simulation without the ligand, and incorporate it afterwards, called implicit ligand sampling (ILS) methods. To compare both approaches performance and to provide a combined protocol to study ligand migration in heme proteins, we performed ILS and multiple steered molecular dynamics (MSMD) free energy calculations of the ligand migration process in three representative and well theoretically and experimentally studied cases that cover a wide range of complex situations presenting a challenging benchmark for the aim of the present work. Our results show that ILS provides a good description of the tunnel topology and a reasonable approximation to the free energy landscape, while MSMD provides more accurate and detailed free energy profile description of each tunnel. Based on these results, a combined strategy is presented for the study of internal ligand migration in heme proteins. Copyright © 2011 Wiley Periodicals, Inc.

  11. Multiple oxygen tension environments reveal diverse patterns of transcriptional regulation in primary astrocytes.

    Directory of Open Access Journals (Sweden)

    Wayne Chadwick

    Full Text Available The central nervous system normally functions at O(2 levels which would be regarded as hypoxic by most other tissues. However, most in vitro studies of neurons and astrocytes are conducted under hyperoxic conditions without consideration of O(2-dependent cellular adaptation. We analyzed the reactivity of astrocytes to 1, 4 and 9% O(2 tensions compared to the cell culture standard of 20% O(2, to investigate their ability to sense and translate this O(2 information to transcriptional activity. Variance of ambient O(2 tension for rat astrocytes resulted in profound changes in ribosomal activity, cytoskeletal and energy-regulatory mechanisms and cytokine-related signaling. Clustering of transcriptional regulation patterns revealed four distinct response pattern groups that directionally pivoted around the 4% O(2 tension, or demonstrated coherent ascending/decreasing gene expression patterns in response to diverse oxygen tensions. Immune response and cell cycle/cancer-related signaling pathway transcriptomic subsets were significantly activated with increasing hypoxia, whilst hemostatic and cardiovascular signaling mechanisms were attenuated with increasing hypoxia. Our data indicate that variant O(2 tensions induce specific and physiologically-focused transcript regulation patterns that may underpin important physiological mechanisms that connect higher neurological activity to astrocytic function and ambient oxygen environments. These strongly defined patterns demonstrate a strong bias for physiological transcript programs to pivot around the 4% O(2 tension, while uni-modal programs that do not, appear more related to pathological actions. The functional interaction of these transcriptional 'programs' may serve to regulate the dynamic vascular responsivity of the central nervous system during periods of stress or heightened activity.

  12. Iterative use of nuclear receptor Nr5a2 regulates multiple stages of liver and pancreas development.

    Science.gov (United States)

    Nissim, Sahar; Weeks, Olivia; Talbot, Jared C; Hedgepeth, John W; Wucherpfennig, Julia; Schatzman-Bone, Stephanie; Swinburne, Ian; Cortes, Mauricio; Alexa, Kristen; Megason, Sean; North, Trista E; Amacher, Sharon L; Goessling, Wolfram

    2016-10-01

    The stepwise progression of common endoderm progenitors into differentiated liver and pancreas organs is regulated by a dynamic array of signals that are not well understood. The nuclear receptor subfamily 5, group A, member 2 gene nr5a2, also known as Liver receptor homolog-1 (Lrh-1) is expressed in several tissues including the developing liver and pancreas. Here, we interrogate the role of Nr5a2 at multiple developmental stages using genetic and chemical approaches and uncover novel pleiotropic requirements during zebrafish liver and pancreas development. Zygotic loss of nr5a2 in a targeted genetic null mutant disrupted the development of the exocrine pancreas and liver, while leaving the endocrine pancreas intact. Loss of nr5a2 abrogated exocrine pancreas markers such as trypsin, while pancreas progenitors marked by ptf1a or pdx1 remained unaffected, suggesting a role for Nr5a2 in regulating pancreatic acinar cell differentiation. In the developing liver, Nr5a2 regulates hepatic progenitor outgrowth and differentiation, as nr5a2 mutants exhibited reduced hepatoblast markers hnf4α and prox1 as well as differentiated hepatocyte marker fabp10a. Through the first in vivo use of Nr5a2 chemical antagonist Cpd3, the iterative requirement for Nr5a2 for exocrine pancreas and liver differentiation was temporally elucidated: chemical inhibition of Nr5a2 function during hepatopancreas progenitor specification was sufficient to disrupt exocrine pancreas formation and enhance the size of the embryonic liver, suggesting that Nr5a2 regulates hepatic vs. pancreatic progenitor fate choice. Chemical inhibition of Nr5a2 at a later time during pancreas and liver differentiation was sufficient to block the formation of mature acinar cells and hepatocytes. These findings define critical iterative and pleiotropic roles for Nr5a2 at distinct stages of pancreas and liver organogenesis, and provide novel perspectives for interpreting the role of Nr5a2 in disease. Copyright © 2016

  13. PI3K Regulates YAP/TAZ in Mammary Tumorigenesis through Multiple Signaling Pathways.

    Science.gov (United States)

    Zhao, Yulei; Montminy, Tess; Azad, Taha; Lightbody, Elizabeth; Hao, Yawei; SenGupta, Sandip; Asselin, Eric; Nicol, Christopher Jb; Yang, Xiaolong

    2018-03-15

    Breast cancer (BC) is a leading cause of death in women worldwide. Active mutations of PI3K catalytic subunit PIK3CA (e.g., H1047R) and amplification of its homolog PIK3CB occur in many BC cases. In recent years, activation of the Transcriptional coactivator with PDZ binding motif (TAZ) and its paralog Yes-associated protein (YAP) have been found to be important for BC development and progression. However, there is no evidence that PI3K interacts with YAP/TAZ in mammary tumorigenesis. Using a systematic gain-of-function screen for kinases involved in mammary tumorigenesis, PIK3CB was identified as a transformation inducing kinase. Phenotypic studies indicate that PIK3CB positively regulates YAP and TAZ to promote transformation and inhibit cell death of mammary cells in vitro. Furthermore, overexpression of PIK3CB together with TAZ rather than PIK3CB or TAZ alone in human non-tumorigenic mammary MCF10A cells causes significant tumor formation in mice. Similarly, PIK3CA-H1047R was also found as a positive regulator of YAP and TAZ in mammary tumorigenesis in vitro. Finally, the regulation of YAP/TAZ by both PIK3CA and PIK3CB occurs through multiple signaling pathways including LATS-dependent and -independent pathways. This study provides the first evidence that Hippo pathway effectors, TAZ and YAP, are critical mediators of PI3K-induced mammary tumorigenesis and function synergistically with PI3K in mammary cell transformation which provides a novel strategy for future targeting of YAP/TAZ alone or in combination with PI3K inhibitors for breast cancer therapy. Copyright ©2018, American Association for Cancer Research.

  14. Solving the Single-Sink, Fixed-Charge, Multiple-Choice Transportation Problem by Dynamic Programming

    DEFF Research Database (Denmark)

    Christensen, Tue; Andersen, Kim Allan; Klose, Andreas

    2013-01-01

    This paper considers a minimum-cost network flow problem in a bipartite graph with a single sink. The transportation costs exhibit a staircase cost structure because such types of transportation cost functions are often found in practice. We present a dynamic programming algorithm for solving...... this so-called single-sink, fixed-charge, multiple-choice transportation problem exactly. The method exploits heuristics and lower bounds to peg binary variables, improve bounds on flow variables, and reduce the state-space variable. In this way, the dynamic programming method is able to solve large...... instances with up to 10,000 nodes and 10 different transportation modes in a few seconds, much less time than required by a widely used mixed-integer programming solver and other methods proposed in the literature for this problem....

  15. Dynamics of quantum Fisher information in a two-level system coupled to multiple bosonic reservoirs

    Science.gov (United States)

    Wang, Guo-You; Guo, You-Neng; Zeng, Ke

    2015-11-01

    We consider the optimal parameter estimation for a two-level system coupled to multiple bosonic reservoirs. By using quantum Fisher information (QFI), we investigate the effect of the Markovian reservoirs’ number N on QFI in both weak and strong coupling regimes for a two-level system surrounded by N zero-temperature reservoirs of field modes initially in the vacua. The results show that the dynamics of QFI non-monotonically decays to zero with revival oscillations at some time in the weak coupling regime depending on the reservoirs’ parameters. Furthermore, we also present the relations between the QFI flow, the flows of energy and information, and the sign of the decay rate to gain insight into the physical processes characterizing the dynamics. Project supported by the Hunan Provincial Innovation Foundation for Postgraduate, China (Grant No. CX2014B194) and the Scientific Research Foundation of Hunan Provincial Education Department, China (Grant No. 13C039).

  16. Dynamics of the nearby multiple stellar systems. The Castor system (ADS 6175)

    International Nuclear Information System (INIS)

    Anosova, Zh.P.; Orlov, V.V.; Chernyshev, M.V.

    1989-01-01

    Statistical analysis of the astrometrical and astrophysical data for the components of the multiple stellar system Castor (ADS 6175) was used to determined the probability of physical connection among components and the dynamical state of this system. The uncertainties of the observational data are taken into account. It is shown that in this visual triple star system the components have a certain gravitational and dynamical connection. The relative orbit of close components AB is elliptical. The probability that the motion of the distant star C in relation to the centre of mass AB is elliptical and the Castor system is stable is 40.7%. The probability that the orbit of C is hyperbolic is 59.1%. The probability that the Castor system may be unstable non-hierarchical is 0.2%

  17. Identifying the Micro-relations Underpinning Familiarity Detection in Dynamic Displays Containing Multiple Objects

    Directory of Open Access Journals (Sweden)

    Jamie S. North

    2017-06-01

    Full Text Available We identified the important micro-relations that are perceived when attempting to recognize patterns in stimuli consisting of multiple dynamic objects. Skilled and less-skilled participants were presented with point light display sequences representing dynamic patterns in an invasion sport and were subsequently required to make familiarity based recognition judgments in three different conditions, each of which contained only a select number of features that were present at initial viewing. No differences in recognition accuracy were observed between skilled and less-skilled participants when just objects located in the periphery were presented. Yet, when presented with the relative motions of two centrally located attacking objects only, skilled participants were significantly more accurate than less-skilled participants and their recognition accuracy improved further when a target object was included against which these relative motions could be judged. Skilled participants can perceive and recognize global patterns on the basis of centrally located relational information.

  18. Robustness analysis of uncertain dynamical neural networks with multiple time delays.

    Science.gov (United States)

    Senan, Sibel

    2015-10-01

    This paper studies the problem of global robust asymptotic stability of the equilibrium point for the class of dynamical neural networks with multiple time delays with respect to the class of slope-bounded activation functions and in the presence of the uncertainties of system parameters of the considered neural network model. By using an appropriate Lyapunov functional and exploiting the properties of the homeomorphism mapping theorem, we derive a new sufficient condition for the existence, uniqueness and global robust asymptotic stability of the equilibrium point for the class of neural networks with multiple time delays. The obtained stability condition basically relies on testing some relationships imposed on the interconnection matrices of the neural system, which can be easily verified by using some certain properties of matrices. An instructive numerical example is also given to illustrate the applicability of our result and show the advantages of this new condition over the previously reported corresponding results. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. A novel multiple cues based image fusing algorithm for high dynamic range image generation

    Science.gov (United States)

    Wu, Xiaojun; Song, Zhan; Yu, Gang; Zheng, Feng

    2012-01-01

    Multiple-exposure-based methods have been an effective means for high dynamic range (HDR) imaging technology. The current methods are greatly dependent on tone mapping, and most of them are unable to accurately recover the local details and colors of the scene. In this work, we present a novel HDR method by using multiple image cues for the image merging process. Firstly, all the images with various exposure times are divided into some uniform sub-regions and an exposure estimation technique is implemented to judge the well exposed one. With all the image blocks have best exposing quality are selected, a blending function is proposed to remove the transition boundaries between these blocks. A fidelity metric index is introduced to assess the final fusion image, and experimental results on public image libraries are given to demonstrate its high performance.

  20. A modified precise integration method for transient dynamic analysis in structural systems with multiple damping models

    Science.gov (United States)

    Ding, Zhe; Li, Li; Hu, Yujin

    2018-01-01

    Sophisticated engineering systems are usually assembled by subcomponents with significantly different levels of energy dissipation. Therefore, these damping systems often contain multiple damping models and lead to great difficulties in analyzing. This paper aims at developing a time integration method for structural systems with multiple damping models. The dynamical system is first represented by a generally damped model. Based on this, a new extended state-space method for the damped system is derived. A modified precise integration method with Gauss-Legendre quadrature is then proposed. The numerical stability and accuracy of the proposed integration method are discussed in detail. It is verified that the method is conditionally stable and has inherent algorithmic damping, period error and amplitude decay. Numerical examples are provided to assess the performance of the proposed method compared with other methods. It is demonstrated that the method is more accurate than other methods with rather good efficiency and the stable condition is easy to be satisfied in practice.

  1. Dynamics of Time Delay-Induced Multiple Synchronous Behaviors in Inhibitory Coupled Neurons

    Science.gov (United States)

    Gu, Huaguang; Zhao, Zhiguo

    2015-01-01

    The inhibitory synapse can induce synchronous behaviors different from the anti-phase synchronous behaviors, which have been reported in recent studies. In the present paper, synchronous behaviors are investigated in the motif model composed of reciprocal inhibitory coupled neurons with endogenous bursting and time delay. When coupling strength is weak, synchronous behavior appears at a single interval of time delay within a bursting period. When coupling strength is strong, multiple synchronous behaviors appear at different intervals of time delay within a bursting period. The different bursting patterns of synchronous behaviors, and time delays and coupling strengths that can induce the synchronous bursting patterns can be well interpreted by the dynamics of the endogenous bursting pattern of isolated neuron, which is acquired by the fast-slow dissection method, combined with the inhibitory coupling current. For an isolated neuron, when a negative impulsive current with suitable strength is applied at different phases of the bursting, multiple different bursting patterns can be induced. For a neuron in the motif, the inhibitory coupling current, of which the application time and strength is modulated by time delay and coupling strength, can cause single or multiple synchronous firing patterns like the negative impulsive current when time delay and coupling strength is suitable. The difference compared to the previously reported multiple synchronous behaviors that appear at time delays wider than a period of the endogenous firing is discussed. The results present novel examples of synchronous behaviors in the neuronal network with inhibitory synapses and provide a reasonable explanation. PMID:26394224

  2. Dynamic trajectory of multiple single-unit activity during working memory task in rats.

    Science.gov (United States)

    Zhang, Xiaofan; Yi, Hu; Bai, Wenwen; Tian, Xin

    2015-01-01

    Working memory plays an important role in complex cognitive tasks. A popular theoretical view is that transient properties of neuronal dynamics underlie cognitive processing. The question raised here as to how the transient dynamics evolve in working memory. To address this issue, we investigated the multiple single-unit activity dynamics in rat medial prefrontal cortex (mPFC) during a Y-maze working memory task. The approach worked by reconstructing state space from delays of the original single-unit firing rate variables, which were further analyzed using kernel principal component analysis (KPCA). Then the neural trajectories were obtained to visualize the multiple single-unit activity. Furthermore, the maximal Lyapunov exponent (MLE) was calculated to quantitatively evaluate the neural trajectories during the working memory task. The results showed that the neuronal activity produced stable and reproducible neural trajectories in the correct trials while showed irregular trajectories in the incorrect trials, which may establish a link between the neurocognitive process and behavioral performance in working memory. The MLEs significantly increased during working memory in the correctly performed trials, indicating an increased divergence of the neural trajectories. In the incorrect trials, the MLEs were nearly zero and remained unchanged during the task. Taken together, the trial-specific neural trajectory provides an effective way to track the instantaneous state of the neuronal population during the working memory task and offers valuable insights into working memory function. The MLE describes the changes of neural dynamics in working memory and may reflect different neuronal population states in working memory.

  3. Ibuprofen regulation of microtubule dynamics in cystic fibrosis epithelial cells.

    Science.gov (United States)

    Rymut, Sharon M; Kampman, Claire M; Corey, Deborah A; Endres, Tori; Cotton, Calvin U; Kelley, Thomas J

    2016-08-01

    High-dose ibuprofen, an effective anti-inflammatory therapy for the treatment of cystic fibrosis (CF), has been shown to preserve lung function in a pediatric population. Despite its efficacy, few patients receive ibuprofen treatment due to potential renal and gastrointestinal toxicity. The mechanism of ibuprofen efficacy is also unclear. We have previously demonstrated that CF microtubules are slower to reform after depolymerization compared with respective wild-type controls. Slower microtubule dynamics in CF cells are responsible for impaired intracellular transport and are related to inflammatory signaling. Here, it is identified that high-dose ibuprofen treatment in both CF cell models and primary CF nasal epithelial cells restores microtubule reformation rates to wild-type levels, as well as induce extension of microtubules to the cell periphery. Ibuprofen treatment also restores microtubule-dependent intracellular transport monitored by measuring intracellular cholesterol transport. These effects are specific to ibuprofen as other cyclooxygenase inhibitors have no effect on these measures. Effects of ibuprofen are mimicked by stimulation of AMPK and blocked by the AMPK inhibitor compound C. We conclude that high-dose ibuprofen treatment enhances microtubule formation in CF cells likely through an AMPK-related pathway. These findings define a potential mechanism to explain the efficacy of ibuprofen therapy in CF. Copyright © 2016 the American Physiological Society.

  4. Voltage regulator for on-board CMS ECAL powering : dynamic stability of the feedback loop

    CERN Document Server

    Wertelaers, P

    2010-01-01

    Traditionally, a capacitor is parallelled to the load of the regulator. Its main function is to steer (limit) the loop bandwidth. An ideal capacitor would provoke near-to-no dynamic stability. A typical remedy, not always elegant, is to select a device with appreciable parasitic series resistance. In this Note, and alternative method is proposed. The CMS ECAL regulator is of adjustable type, and adding a small capacitor at the divider there, brings about a "lead" type control action.

  5. Detection of fast oscillating magnetic fields using dynamic multiple TR imaging and Fourier analysis.

    Directory of Open Access Journals (Sweden)

    Ki Hwan Kim

    Full Text Available Neuronal oscillations produce oscillating magnetic fields. There have been trials to detect neuronal oscillations using MRI, but the detectability in in vivo is still in debate. Major obstacles to detecting neuronal oscillations are (i weak amplitudes, (ii fast oscillations, which are faster than MRI temporal resolution, and (iii random frequencies and on/off intervals. In this study, we proposed a new approach for direct detection of weak and fast oscillating magnetic fields. The approach consists of (i dynamic acquisitions using multiple times to repeats (TRs and (ii an expanded frequency spectral analysis. Gradient echo echo-planar imaging was used to test the feasibility of the proposed approach with a phantom generating oscillating magnetic fields with various frequencies and amplitudes and random on/off intervals. The results showed that the proposed approach could precisely detect the weak and fast oscillating magnetic fields with random frequencies and on/off intervals. Complex and phase spectra showed reliable signals, while no meaningful signals were observed in magnitude spectra. A two-TR approach provided an absolute frequency spectrum above Nyquist sampling frequency pixel by pixel with no a priori target frequency information. The proposed dynamic multiple-TR imaging and Fourier analysis are promising for direct detection of neuronal oscillations and potentially applicable to any pulse sequences.

  6. Hybrid integer coded differential evolution - dynamic programming approach for economic load dispatch with multiple fuel options

    Energy Technology Data Exchange (ETDEWEB)

    Balamurugan, R.; Subramanian, S. [Department of Electrical Engineering, Annamalai University, Annamalai Nagar 608 002 (India)

    2008-04-15

    This paper presents a novel and efficient approach through a hybrid integer coded differential evolution - dynamic programming (ICDEDP) scheme to solve the economic dispatch (ED) problem with multiple fuel options. A dynamic programming (DP) based simplified recursive algorithm is developed for optimal scheduling of the generating units in the ED problem. The proposed hybrid scheme is developed in such a way that an integer coded differential evolution (ICDE) is acting as a main optimizer to identify the optimal fuel options, and the DP is used to find the fitness of each agent in the population of the ICDE, which makes a quick decision to direct the search towards the optimal region. The hybrid ICDEDP decision vector consists of a sequence of integer numbers representing the fuel options of each unit to optimize quality of search and computation time. A gene swap operator is introduced in the proposed algorithm to improve its convergence characteristics. In order to show the efficiency and effectiveness, the proposed hybrid ICDEDP approach has been examined and tested with numerical results using the ten generation unit economic dispatch problem with multiple fuel options. The test result shows that the proposed hybrid ICDEDP algorithm has high quality solution, superior convergence characteristics and shorter computation time. (author)

  7. Dynamic analysis and evolution of mixed materials bombarded with multiple ions beams

    International Nuclear Information System (INIS)

    Sizyuk, T.; Hassanein, A.

    2010-01-01

    Materials modification and response to the impact of energetic particles is an important ongoing research area in several applications. This includes both experimental and theoretical work. We updated and improved our models for the simulation of Ion Transport in Materials and Compounds (ITMC-DYN), part of HEIGHTS package, to now include dynamic changing of materials composition as result of multiple ion beams bombardment and target atoms mixing, segregation, and diffusion. Implemented models consider detail processes of simultaneous and multiple ions penetration and mixing, scattering, reflection, physical and chemical sputtering of composite material atoms, dynamic surface evolution/modification, thermal diffusion, and surface segregation and recombination of species in multicomponent alloys. For benchmarking of the models we compared our simulations results with several recent experimental data for nanoapplications and for the developments of future fusion energy systems. Simulation of tungsten surface evolution and modification under the impact of hydrogen ions with carbon impurities demonstrated good agreement with recent experiments. Details of surface erosion and conditions for blisters formation as a function of fluence and material temperature were also analyzed and explained.

  8. Detection of fast oscillating magnetic fields using dynamic multiple TR imaging and Fourier analysis.

    Science.gov (United States)

    Kim, Ki Hwan; Heo, Hyo-Im; Park, Sung-Hong

    2018-01-01

    Neuronal oscillations produce oscillating magnetic fields. There have been trials to detect neuronal oscillations using MRI, but the detectability in in vivo is still in debate. Major obstacles to detecting neuronal oscillations are (i) weak amplitudes, (ii) fast oscillations, which are faster than MRI temporal resolution, and (iii) random frequencies and on/off intervals. In this study, we proposed a new approach for direct detection of weak and fast oscillating magnetic fields. The approach consists of (i) dynamic acquisitions using multiple times to repeats (TRs) and (ii) an expanded frequency spectral analysis. Gradient echo echo-planar imaging was used to test the feasibility of the proposed approach with a phantom generating oscillating magnetic fields with various frequencies and amplitudes and random on/off intervals. The results showed that the proposed approach could precisely detect the weak and fast oscillating magnetic fields with random frequencies and on/off intervals. Complex and phase spectra showed reliable signals, while no meaningful signals were observed in magnitude spectra. A two-TR approach provided an absolute frequency spectrum above Nyquist sampling frequency pixel by pixel with no a priori target frequency information. The proposed dynamic multiple-TR imaging and Fourier analysis are promising for direct detection of neuronal oscillations and potentially applicable to any pulse sequences.

  9. Analysis of the Dynamical Instability of Several Multiple Stars with Weak Hierarchy

    Science.gov (United States)

    Zhuchkov, R. Ya.; Orlov, V. V.

    2005-04-01

    The dynamical stability of 16 multiple stars is analyzed using Monte Carlo simulations with allowance for the errors in the observational data. The analysis was carried out by varying the uncertainties in the initial observational data. Six different stability criteria were considered, and the dynamical evolution was studied using numerical simulations. Eleven of the systems are probably stable, whereas five systems (HD 40887, HD 136176, HD 150680, HD 217675, and HD 222326) are probably unstable (the probability that they are unstable is 0.94 or more accordingt o the results of forward and backward simulations over intervals of 106 yr). The results of the simulations were most consistent with the criteria of Mardling-Aarseth (the correlation coefficient between the probabilities of disruption inferred from the stability criterion and numerical integration was r = 0.998), Valtonen-Karttunen (r = 0.998), and Eggleton-Kiseleva (r = 0.997). In about 92 93% of all cases, these criteria yield results that are consistent with the numerical simulations. These criteria also yield high disruption probabilities for the unstable systems. Scenarios for the formation of such systems are discussed: temporary capture of a field star by a close binary, perturbation of a stable multiple system by a massive field object, and disruption of small stellar groups or clusters. The probabilities that these scenarios are realized are analyzed.

  10. A Comparison of Combustion Dynamics for Multiple 7-Point Lean Direct Injection Combustor Configurations

    Science.gov (United States)

    Tacina, K. M.; Hicks, Y. R.

    2017-01-01

    The combustion dynamics of multiple 7-point lean direct injection (LDI) combustor configurations are compared. LDI is a fuel-lean combustor concept for aero gas turbine engines in which multiple small fuel-air mixers replace one traditionally-sized fuel-air mixer. This 7-point LDI configuration has a circular cross section, with a center (pilot) fuel-air mixer surrounded by six outer (main) fuel-air mixers. Each fuel-air mixer consists of an axial air swirler followed by a converging-diverging venturi. A simplex fuel injector is inserted through the center of the air swirler, with the fuel injector tip located near the venturi throat. All 7 fuel-air mixers are identical except for the swirler blade angle, which varies with the configuration. Testing was done in a 5-atm flame tube with inlet air temperatures from 600 to 800 F and equivalence ratios from 0.4 to 0.7. Combustion dynamics were measured using a cooled PCB pressure transducer flush-mounted in the wall of the combustor test section.

  11. The Assessment of Cognitive Emotion Regulation Strategies, Sensory Processing Sensitivity and Anxiety Sensitivity in Patients with Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Esmeil Soleymani

    2016-11-01

    Full Text Available Abstract Background: The purpose of this study was to compare the cognitive emotional regulation strategies, sensory processing sensitivity and anxiety sensitivity in patients with multiple sclerosis and normal people. Materials and Methods: Statistical population of this study was all of patients with multiple sclerosis that referred to M.S association of Iran in the tehran. Sample of this study was 30 individuals of patients with multiple sclerosis selected by available sampling method and were matched with 30 individuals of normal people. Two groups completed cognitive emotion regulation, high sensory processing sensitivity and anxiety sensitivity questionnaires. Data were analyzed by one-way analysis of variance and Multivariate Analysis of Variance. Results: The results indicated that there is significant difference between two groups in view of cognitive emotion regulation strategies in which the mean of scores of patients with multiple sclerosis in maladaptive strategies of self- blame, catastrophizing and other blame were more than normal people and mean of scores of them in adaptive strategies of positive refocusing, positive reappraisal and putting into perspective were less than normal people. The results also indicated that there is a significant difference between two groups in anxiety sensitivity and sensory processing sensitivity. Conclusion: The most of emotional problems in patients with multiple sclerosis can be the result of more application of maladaptive strategies of cognitive emotion regulation, high sensory processing sensitivity and high anxiety sensitivity.

  12. Multiplicity

    Science.gov (United States)

    1991-04-01

    Virginia, 388 U.S. 1 (1967)(criminal statute prohibiting interracial marriages held unconstitutional violation of the Equal Protection and Due Process...such sentences does not violate the Constitution."°2 7 In effect , the double jeopardy protection from multiple punishments is coextensive with...unaware of what it accomplished . . . . In effect , the Blockburger test establishes a presumption of legislative intent: if each of two statutes

  13. Combinatorial Optimization Algorithms for Dynamic Multiple Fault Diagnosis in Automotive and Aerospace Applications

    Science.gov (United States)

    Kodali, Anuradha

    In this thesis, we develop dynamic multiple fault diagnosis (DMFD) algorithms to diagnose faults that are sporadic and coupled. Firstly, we formulate a coupled factorial hidden Markov model-based (CFHMM) framework to diagnose dependent faults occurring over time (dynamic case). Here, we implement a mixed memory Markov coupling model to determine the most likely sequence of (dependent) fault states, the one that best explains the observed test outcomes over time. An iterative Gauss-Seidel coordinate ascent optimization method is proposed for solving the problem. A soft Viterbi algorithm is also implemented within the framework for decoding dependent fault states over time. We demonstrate the algorithm on simulated and real-world systems with coupled faults; the results show that this approach improves the correct isolation rate as compared to the formulation where independent fault states are assumed. Secondly, we formulate a generalization of set-covering, termed dynamic set-covering (DSC), which involves a series of coupled set-covering problems over time. The objective of the DSC problem is to infer the most probable time sequence of a parsimonious set of failure sources that explains the observed test outcomes over time. The DSC problem is NP-hard and intractable due to the fault-test dependency matrix that couples the failed tests and faults via the constraint matrix, and the temporal dependence of failure sources over time. Here, the DSC problem is motivated from the viewpoint of a dynamic multiple fault diagnosis problem, but it has wide applications in operations research, for e.g., facility location problem. Thus, we also formulated the DSC problem in the context of a dynamically evolving facility location problem. Here, a facility can be opened, closed, or can be temporarily unavailable at any time for a given requirement of demand points. These activities are associated with costs or penalties, viz., phase-in or phase-out for the opening or closing of a

  14. Late multiple organ surge in interferon-regulated target genes characterizes staphylococcal enterotoxin B lethality.

    Directory of Open Access Journals (Sweden)

    Gabriela A Ferreyra

    Full Text Available BACKGROUND: Bacterial superantigens are virulence factors that cause toxic shock syndrome. Here, the genome-wide, temporal response of mice to lethal intranasal staphylococcal enterotoxin B (SEB challenge was investigated in six tissues. RESULTS: The earliest responses and largest number of affected genes occurred in peripheral blood mononuclear cells (PBMC, spleen, and lung tissues with the highest content of both T-cells and monocyte/macrophages, the direct cellular targets of SEB. In contrast, the response of liver, kidney, and heart was delayed and involved fewer genes, but revealed a dominant genetic program that was seen in all 6 tissues. Many of the 85 uniquely annotated transcripts participating in this shared genomic response have not been previously linked to SEB. Nine of the 85 genes were subsequently confirmed by RT-PCR in every tissue/organ at 24 h. These 85 transcripts, up-regulated in all tissues, annotated to the interferon (IFN/antiviral-response and included genes belonging to the DNA/RNA sensing system, DNA damage repair, the immunoproteasome, and the ER/metabolic stress-response and apoptosis pathways. Overall, this shared program was identified as a type I and II interferon (IFN-response and the promoters of these genes were highly enriched for IFN regulatory matrices. Several genes whose secreted products induce the IFN pathway were up-regulated at early time points in PBMCs, spleen, and/or lung. Furthermore, IFN regulatory factors including Irf1, Irf7 and Irf8, and Zbp1, a DNA sensor/transcription factor that can directly elicit an IFN innate immune response, participated in this host-wide SEB signature. CONCLUSION: Global gene-expression changes across multiple organs implicated a host-wide IFN-response in SEB-induced death. Therapies aimed at IFN-associated innate immunity may improve outcome in toxic shock syndromes.

  15. Dynamic activity of NF-κB in multiple trauma patients and protective effects of ulinastain

    Directory of Open Access Journals (Sweden)

    LI Jun

    2012-02-01

    Full Text Available 【Abstract】Objective: To investigate the dynamic activity of NF-κB at the early stage of injury in multiple trauma patients and the protective effects of ulinastain. Methods: From January 2008 to May 2010, patients with multiple traumas admitted to our emergency department were enrolled in this study. Their age varied from 20-55 years. All enrolled patients were assigned randomly into control group (26 cases of multiple injury without ulinastain treatment, ulinastain group (25 cases of multiple injury with ulinastain treatment, and mild injury group (20 cases for basic control. The inclusion criteria for mild injury group were AIS-2005≤3, single wound, previously healthy inhospital patients without the history of surgical intervention. In addition to routine treatment, patients in ulinastain group were intravenously injected 200 000 IU of ulinastain dissolved in 100 ml of normal saline within 12 hours after injury and subsequently injected at the interval of every 8 hours for 7 days. NF-κB activity in monocytes and the level of TNF? IL-1, IL? in serum on admission (day 0, day 1, 2, 3, 4, and 7 were measured. Data were compared and analyzed between different groups. Results: NF-κB activity in monocytes and TNF? IL-1 and IL? of these patients reached peak levels at 24 hour after trauma, with gradual decrease to normal at 72 hour after trauma. NF-κB activity and levels of TNF? IL-1 and IL? were lower in ulinastain group than control one, without any significant difference between the two groups. The mean duration for systemic inflammatory response syndrome and multiple organ dysfunction syndrome was 7 d?.1 d and 10 d?.5 d in ulinastain group and control group respectively, and showed a significant difference. Conclusions: NF-κB activity in monocytes and the levels of inflammatory cytokines in multiply injured patients increased transiently at the early stage of trauma. Ulinastain may shorten the duration of systemic inflammatory

  16. Formation Learning Control of Multiple Autonomous Underwater Vehicles With Heterogeneous Nonlinear Uncertain Dynamics.

    Science.gov (United States)

    Yuan, Chengzhi; Licht, Stephen; He, Haibo

    2017-09-26

    In this paper, a new concept of formation learning control is introduced to the field of formation control of multiple autonomous underwater vehicles (AUVs), which specifies a joint objective of distributed formation tracking control and learning/identification of nonlinear uncertain AUV dynamics. A novel two-layer distributed formation learning control scheme is proposed, which consists of an upper-layer distributed adaptive observer and a lower-layer decentralized deterministic learning controller. This new formation learning control scheme advances existing techniques in three important ways: 1) the multi-AUV system under consideration has heterogeneous nonlinear uncertain dynamics; 2) the formation learning control protocol can be designed and implemented by each local AUV agent in a fully distributed fashion without using any global information; and 3) in addition to the formation control performance, the distributed control protocol is also capable of accurately identifying the AUVs' heterogeneous nonlinear uncertain dynamics and utilizing experiences to improve formation control performance. Extensive simulations have been conducted to demonstrate the effectiveness of the proposed results.

  17. Understanding the free energy barrier and multiple timescale dynamics of charge separation in organic photovoltaic cells

    Science.gov (United States)

    Yan, Yaming; Song, Linze; Shi, Qiang

    2018-02-01

    By employing several lattice model systems, we investigate the free energy barrier and real-time dynamics of charge separation in organic photovoltaic (OPV) cells. It is found that the combined effects of the external electric field, entropy, and charge delocalization reduce the free energy barrier significantly. The dynamic disorder reduces charge carrier delocalization and results in the increased charge separation barrier, while the effect of static disorder is more complicated. Simulation of the real-time dynamics indicates that the free charge generation process involves multiple time scales, including an ultrafast component within hundreds of femtoseconds, an intermediate component related to the relaxation of the hot charge transfer (CT) state, and a slow component on the time scale of tens of picoseconds from the thermally equilibrated CT state. Effects of hot exciton dissociation as well as its dependence on the energy offset between the Frenkel exciton and the CT state are also analyzed. The current results indicate that only a small energy offset between the band gap and the lowest energy CT state is needed to achieve efficient free charge generation in OPV devices, which agrees with recent experimental findings.

  18. Understanding the free energy barrier and multiple timescale dynamics of charge separation in organic photovoltaic cells.

    Science.gov (United States)

    Yan, Yaming; Song, Linze; Shi, Qiang

    2018-02-28

    By employing several lattice model systems, we investigate the free energy barrier and real-time dynamics of charge separation in organic photovoltaic (OPV) cells. It is found that the combined effects of the external electric field, entropy, and charge delocalization reduce the free energy barrier significantly. The dynamic disorder reduces charge carrier delocalization and results in the increased charge separation barrier, while the effect of static disorder is more complicated. Simulation of the real-time dynamics indicates that the free charge generation process involves multiple time scales, including an ultrafast component within hundreds of femtoseconds, an intermediate component related to the relaxation of the hot charge transfer (CT) state, and a slow component on the time scale of tens of picoseconds from the thermally equilibrated CT state. Effects of hot exciton dissociation as well as its dependence on the energy offset between the Frenkel exciton and the CT state are also analyzed. The current results indicate that only a small energy offset between the band gap and the lowest energy CT state is needed to achieve efficient free charge generation in OPV devices, which agrees with recent experimental findings.

  19. A study on the multiple dynamic wavelength distribution for gigabit capable passive optical networks

    Directory of Open Access Journals (Sweden)

    Gustavo Adolfo Puerto Leguizamón

    2014-04-01

    Full Text Available This paper presents a data traffic based study aiming at evaluating the impact of dynamic wavelength allocation on a Gigabit capable Passive Optical Network (GPON. In Passive Optical Networks (PON, an Optical Line Terminal (OLT feeds different PONs in such a way that a given wavelength channel is evenly distributed between the Optical Network Units (ONU at each PON. However, PONs do not specify any kind of dynamic behavior on the way the wavelengths are allocated in the network, a completely static distribution is implemented instead. In thispaper we evaluate the network performance in terms of packet losses and throughput for a number of ONUs being out-of-profile while featuring a given percentage of traffic in excess for a fixed wavelength distribution and for multiple dynamic wavelength allocation. Results show that for a multichannel operation with four wavelengths, the network throughput increases up to a rough value of 19% while the packet losses drop from 22 % to 1.8 % as compared with a static wavelength distribution.

  20. Capital Regulation, Liquidity Requirements and Taxation in a Dynamic Model of Banking

    NARCIS (Netherlands)

    Di Nicolo, G.; Gamba, A.; Lucchetta, M.

    2011-01-01

    This paper formulates a dynamic model of a bank exposed to both credit and liquidity risk, which can resolve financial distress in three costly forms: fire sales, bond issuance ad equity issuance. We use the model to analyze the impact of capital regulation, liquidity requirements and taxation on

  1. Capital Regulation, Liquidity Requirements and Taxation in a Dynamic Model of Banking

    NARCIS (Netherlands)

    Di Nicolo, G.; Gamba, A.; Lucchetta, M.

    2011-01-01

    This paper formulates a dynamic model of a bank exposed to both credit and liquidity risk, which can resolve financial distress in three costly forms: fire sales, bond issuance and equity issuance. We use the model to analyze the impact of capital regulation, liquidity requirements and taxation on

  2. Dynamic Scaffolding of Socially Regulated Learning in a Computer-Based Learning Environment

    NARCIS (Netherlands)

    Molenaar, I.; Roda, Claudia; van Boxtel, Carla A.M.; Sleegers, P.J.C.

    2012-01-01

    The aim of this study is to test the effects of dynamically scaffolding social regulation of middle school students working in a computer-based learning environment. Dyads in the scaffolding condition (N = 56) are supported with computer-generated scaffolds and students in the control condition (N =

  3. Insulin regulates multiple signaling pathways leading to monocyte/macrophage chemotaxis into the wound tissue

    Directory of Open Access Journals (Sweden)

    Yan Liu

    2018-01-01

    Full Text Available Wound healing is a complex process that involves sequential phases that overlap in time and space and affect each other dynamically at the gene and protein levels. We previously showed that insulin accelerates wound healing by stimulating faster and regenerative healing. One of the processes that insulin stimulates is an increase in monocyte/macrophage chemotaxis. In this study, we performed experiments in vivo and in vitro to elucidate the signaling transduction pathways that are involved in insulin-induced monocyte/macrophage chemotaxis. We found that insulin stimulates THP-1 cell chemotaxis in a dose-dependent and insulin receptor-dependent manner. We also show that the kinases PI3K-Akt, SPAK/JNK, and p38 MAPK are key molecules in the insulin-induced signaling pathways that lead to chemoattraction of the THP-1 cell. Furthermore, both PI3K-Akt and SPAK/JNK signaling involve Rac1 activation, an important molecule in regulating cell motility. Indeed, topical application of Rac1 inhibitor at an early stage during the healing process caused delayed and impaired healing even in the presence of insulin. These results delineate cell and molecular mechanisms involved in insulin-induced chemotaxis of monocyte/macrophage, cells that are critical for proper healing.

  4. ABT737 enhances cholangiocarcinoma sensitivity to cisplatin through regulation of mitochondrial dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Fan, Zhongqi [Department of Hepatobiliary & Pancreas Surgery, The First Hospital, Jilin University, Changchun, Jilin 130021 (China); Yu, Huimei [Department of Pathophysiology, School of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021 (China); Cui, Ni [Bethune Medical College, Jilin University, Changchun, Jilin 130021 (China); Kong, Xianggui; Liu, Xiaomin; Chang, Yulei [State Key Laboratory of Luminescence and Applications, Changchun Institute of Optics, Fine Mechanics and Physics, Chinese Academy of Sciences, Changchun, Jilin 130033 (China); Wu, Yao [Department of Pathophysiology, School of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021 (China); Sun, Liankun, E-mail: sunlk@jlu.edu.cn [Department of Pathophysiology, School of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021 (China); Wang, Guangyi, E-mail: wgymd@sina.com [Department of Hepatobiliary & Pancreas Surgery, The First Hospital, Jilin University, Changchun, Jilin 130021 (China)

    2015-07-01

    Cholangiocarcinoma responses weakly to cisplatin. Mitochondrial dynamics participate in the response to various stresses, and mainly involve mitophagy and mitochondrial fusion and fission. Bcl-2 family proteins play critical roles in orchestrating mitochondrial dynamics, and are involved in the resistance to cisplatin. Here we reported that ABT737, combined with cisplatin, can promote cholangiocarcinoma cells to undergo apoptosis. We found that the combined treatment decreased the Mcl-1 pro-survival form and increased Bak. Cells undergoing cisplatin treatment showed hyperfused mitochondria, whereas fragmentation was dominant in the mitochondria of cells exposed to the combined treatment, with higher Fis1 levels, decreased Mfn2 and OPA1 levels, increased ratio of Drp1 60 kD to 80 kD form, and more Drp1 located on mitochondria. More p62 aggregates were observed in cells with fragmented mitochondria, and they gradually translocated to mitochondria. Mitophagy was induced by the combined treatment. Knockdown p62 decreased the Drp1 ratio, increased Tom20, and increased cell viability. Our data indicated that mitochondrial dynamics play an important role in the response of cholangiocarcinoma to cisplatin. ABT737 might enhance cholangiocarcinoma sensitivity to cisplatin through regulation of mitochondrial dynamics and the balance within Bcl-2 family proteins. Furthermore, p62 seems to be critical in the regulation of mitochondrial dynamics. - Highlights: • Cholangiocarcinoma may adapt to cisplatin through mitochondrial fusion. • ABT737 sensitizes cholangiocarcinoma to cisplatin by promoting fission and mitophagy. • p62 might participate in the regulation of mitochondrial fission and mitophagy.

  5. ABT737 enhances cholangiocarcinoma sensitivity to cisplatin through regulation of mitochondrial dynamics

    International Nuclear Information System (INIS)

    Fan, Zhongqi; Yu, Huimei; Cui, Ni; Kong, Xianggui; Liu, Xiaomin; Chang, Yulei; Wu, Yao; Sun, Liankun; Wang, Guangyi

    2015-01-01

    Cholangiocarcinoma responses weakly to cisplatin. Mitochondrial dynamics participate in the response to various stresses, and mainly involve mitophagy and mitochondrial fusion and fission. Bcl-2 family proteins play critical roles in orchestrating mitochondrial dynamics, and are involved in the resistance to cisplatin. Here we reported that ABT737, combined with cisplatin, can promote cholangiocarcinoma cells to undergo apoptosis. We found that the combined treatment decreased the Mcl-1 pro-survival form and increased Bak. Cells undergoing cisplatin treatment showed hyperfused mitochondria, whereas fragmentation was dominant in the mitochondria of cells exposed to the combined treatment, with higher Fis1 levels, decreased Mfn2 and OPA1 levels, increased ratio of Drp1 60 kD to 80 kD form, and more Drp1 located on mitochondria. More p62 aggregates were observed in cells with fragmented mitochondria, and they gradually translocated to mitochondria. Mitophagy was induced by the combined treatment. Knockdown p62 decreased the Drp1 ratio, increased Tom20, and increased cell viability. Our data indicated that mitochondrial dynamics play an important role in the response of cholangiocarcinoma to cisplatin. ABT737 might enhance cholangiocarcinoma sensitivity to cisplatin through regulation of mitochondrial dynamics and the balance within Bcl-2 family proteins. Furthermore, p62 seems to be critical in the regulation of mitochondrial dynamics. - Highlights: • Cholangiocarcinoma may adapt to cisplatin through mitochondrial fusion. • ABT737 sensitizes cholangiocarcinoma to cisplatin by promoting fission and mitophagy. • p62 might participate in the regulation of mitochondrial fission and mitophagy

  6. Layered dynamic regulation for improving metabolic pathway productivity inEscherichia coli.

    Science.gov (United States)

    Doong, Stephanie J; Gupta, Apoorv; Prather, Kristala L J

    2018-03-20

    Microbial production of value-added chemicals from biomass is a sustainable alternative to chemical synthesis. To improve product titer, yield, and selectivity, the pathways engineered into microbes must be optimized. One strategy for optimization is dynamic pathway regulation, which modulates expression of pathway-relevant enzymes over the course of fermentation. Metabolic engineers have used dynamic regulation to redirect endogenous flux toward product formation, balance the production and consumption rates of key intermediates, and suppress production of toxic intermediates until later in the fermentation. Most cases, however, have utilized a single strategy for dynamically regulating pathway fluxes. Here we layer two orthogonal, autonomous, and tunable dynamic regulation strategies to independently modulate expression of two different enzymes to improve production of D-glucaric acid from a heterologous pathway. The first strategy uses a previously described pathway-independent quorum sensing system to dynamically knock down glycolytic flux and redirect carbon into production of glucaric acid, thereby switching cells from "growth" to "production" mode. The second strategy, developed in this work, uses a biosensor for myo -inositol (MI), an intermediate in the glucaric acid production pathway, to induce expression of a downstream enzyme upon sufficient buildup of MI. The latter, pathway-dependent strategy leads to a 2.5-fold increase in titer when used in isolation and a fourfold increase when added to a strain employing the former, pathway-independent regulatory system. The dual-regulation strain produces nearly 2 g/L glucaric acid, representing the highest glucaric acid titer reported to date in Escherichia coli K-12 strains.

  7. Bayesian state space models for dynamic genetic network construction across multiple tissues.

    Science.gov (United States)

    Liang, Yulan; Kelemen, Arpad

    2016-08-01

    Construction of gene-gene interaction networks and potential pathways is a challenging and important problem in genomic research for complex diseases while estimating the dynamic changes of the temporal correlations and non-stationarity are the keys in this process. In this paper, we develop dynamic state space models with hierarchical Bayesian settings to tackle this challenge for inferring the dynamic profiles and genetic networks associated with disease treatments. We treat both the stochastic transition matrix and the observation matrix time-variant and include temporal correlation structures in the covariance matrix estimations in the multivariate Bayesian state space models. The unevenly spaced short time courses with unseen time points are treated as hidden state variables. Hierarchical Bayesian approaches with various prior and hyper-prior models with Monte Carlo Markov Chain and Gibbs sampling algorithms are used to estimate the model parameters and the hidden state variables. We apply the proposed Hierarchical Bayesian state space models to multiple tissues (liver, skeletal muscle, and kidney) Affymetrix time course data sets following corticosteroid (CS) drug administration. Both simulation and real data analysis results show that the genomic changes over time and gene-gene interaction in response to CS treatment can be well captured by the proposed models. The proposed dynamic Hierarchical Bayesian state space modeling approaches could be expanded and applied to other large scale genomic data, such as next generation sequence (NGS) combined with real time and time varying electronic health record (EHR) for more comprehensive and robust systematic and network based analysis in order to transform big biomedical data into predictions and diagnostics for precision medicine and personalized healthcare with better decision making and patient outcomes.

  8. Microglial morphology and dynamic behavior is regulated by ionotropic glutamatergic and GABAergic neurotransmission.

    Directory of Open Access Journals (Sweden)

    Aurora M Fontainhas

    Full Text Available PURPOSE: Microglia represent the primary resident immune cells in the CNS, and have been implicated in the pathology of neurodegenerative diseases. Under basal or "resting" conditions, microglia possess ramified morphologies and exhibit dynamic surveying movements in their processes. Despite the prominence of this phenomenon, the function and regulation of microglial morphology and dynamic behavior are incompletely understood. We investigate here whether and how neurotransmission regulates "resting" microglial morphology and behavior. METHODS: We employed an ex vivo mouse retinal explant system in which endogenous neurotransmission and dynamic microglial behavior are present. We utilized live-cell time-lapse confocal imaging to study the morphology and behavior of GFP-labeled retinal microglia in response to neurotransmitter agonists and antagonists. Patch clamp electrophysiology and immunohistochemical localization of glutamate receptors were also used to investigate direct-versus-indirect effects of neurotransmission by microglia. RESULTS: Retinal microglial morphology and dynamic behavior were not cell-autonomously regulated but are instead modulated by endogenous neurotransmission. Morphological parameters and process motility were differentially regulated by different modes of neurotransmission and were increased by ionotropic glutamatergic neurotransmission and decreased by ionotropic GABAergic neurotransmission. These neurotransmitter influences on retinal microglia were however unlikely to be directly mediated; local applications of neurotransmitters were unable to elicit electrical responses on microglia patch-clamp recordings and ionotropic glutamatergic receptors were not located on microglial cell bodies or processes by immunofluorescent labeling. Instead, these influences were mediated indirectly via extracellular ATP, released in response to glutamatergic neurotransmission through probenecid-sensitive pannexin hemichannels

  9. Stressing "Escherichia coli" to Educate Students about Research: A CURE to Investigate Multiple Levels of Gene Regulation

    Science.gov (United States)

    McDonough, Janet; Goudsouzian, Lara K.; Papaj, Agllai; Maceli, Ashley R.; Klepac-Ceraj, Vanja; Peterson, Celeste N.

    2017-01-01

    Course-based undergraduate research experiences (CUREs) have been shown to increase student retention and learning in the biological sciences. Most CURES cover only one aspect of gene regulation, such as transcriptional control. Here we present a new inquiry-based lab that engages understanding of gene expression from multiple perspectives.…

  10. Fixed fields, multiple arcs, intensity modulation, and dynamic arcs: (when should I use which and why?)

    International Nuclear Information System (INIS)

    Bova, F.J.

    2001-01-01

    Full text: The historical development of radiosurgery was heavily influenced by the designs of the first commercially successful radiosurgery unit, The Leksel Gamma-Knife. The use of non-coplanar circular radiation beams produced an isodose distribution that was accurate and exhibited and extremely high dose gradient. The linac designs that followed mimicked this beam design and arrangement. The non-coplanar arcs used by most radiosurgical systems are designed to provide an isotropic set of entrance and exit beams. The key to maintaining these dose concentration and gradient has been to provide a sufficient number of beams to allow unique, non-overlapping, entrance and exit pathways. While several systems have advocated alternative beam arrangements no metric for the unique properties of the historic radiosurgery distributions has been available. Because radiosurgery, like other radiation treatments, is based up on a clinical art it is important to provide such a metric to judge alternative treatment strategies. Such a metric was developed. A test involving patients taken from our databases were used to test Fixed Fields, Multiple Arcs, Intensity Modulation and Dynamic Arc treatment plans. To judge the goodness of a radiosurgery plan an index that measured dose conformality and dose gradient was developed. This index, termed the UF index, uses a routine measure of conformality to judge how much normal tissue is within the prescription isodose shell. The index also measures the dose gradient by computing the volume between the treatment isodose shell and the isodose shell that represents one half the value of the treatment isodose. This volume is then converted to an average 3D shell around the treatment isodose and the radius of this shell computed. The index is formulated so that it increases with increasing conformality and increases as the radius of the shell containing the dose gradient decreases. This provides the highest score to treatment with increasing

  11. The Zymomonas mobilis regulator hfq contributes to tolerance against multiple lignocellulosic pretreatment inhibitors

    Directory of Open Access Journals (Sweden)

    Lu Tse-Yuan S

    2010-05-01

    mutant construction in Z. mobilis, and constructed a Gateway compatible expression plasmid for use in Z. mobilis for the first time. We have also used genetics to show Z. mobilis Hfq and S. cerevisiae Lsm proteins play important roles in resisting multiple, important industrially relevant inhibitors. The conserved nature of this global regulator offers the potential to apply insights from these fundamental studies for further industrial strain development.

  12. The persistent organochlorine pesticide endosulfan modulates multiple epigenetic regulators with oncogenic potential in MCF-7 cells.

    Science.gov (United States)

    Ghosh, Krishna; Chatterjee, Biji; Jayaprasad, Aparna Geetha; Kanade, Santosh R

    2018-05-15

    Environmental cues and chemicals can potentially modulate the phenotypic expression of genome through alterations in the epigenetic mechanisms. Endosulfan is one of the extensively used organochlorine pesticides around the world which is known for its endocrine, neuro- and reproductive toxicity. This study was aimed to investigate the potential of α-endosulfan in modulation of multiple epigenetic enzymes in MCF-7 cells. The cells were treated with DMSO (control) or α-endosulfan (1 and 10μM) and the expression of various epigenetic enzymes was assayed by real-time PCR and immunoblotting, in addition to their activity assays. The results shows α-endosulfan, at 1 and 10μM concentration, significantly promoted viability of MCF-7 cells compared to untreated cells after 24h. The expression of DNA methyltransferases (DNMTs) was upregulated while the global DNA methylation status was initially affected, but later recovered. Total intracellular histone deacetylase (HDAC) activity was found to be significantly increased which was correlated with upregulation of class I HDACs (HDAC 1 and 3) while no significant alteration in the other HDAC classes was observed. The expression and activity of arginine and lysine methylation enzymes, protein arginine methyltransferase 5 (PRMT5) and Enhancer of Zeste homolog 2 (EZH2), respectively, were also found to be modulated by α-endosulfan. We found increased expression of histones H3 and H4, trimethylated H3K27 (product of EZH2), symmetric dimethylation of H4R3 (product of PRMT5) and five different (unidentified) proteins whose arginine residues are symmetrically dimethylated (by increased level of PRMT5) were enhanced in response to 10μM α-endosulfan after 24h exposure window. Moreover, overexpression of basal level of estrogen receptor alpha (ERα), suggests estrogenicity of α-endosulfan. In summary, our results shows modulatory impact of α-endosulfan on multiple cellular epigenetic regulators, known to possess oncogenic

  13. Motivational dynamics of eating regulation: a self-determination theory perspective

    Science.gov (United States)

    2012-01-01

    Within Western society, many people have difficulties adequately regulating their eating behaviors and weight. Although the literature on eating regulation is vast, little attention has been given to motivational dynamics involved in eating regulation. Grounded in Self-Determination Theory (SDT), the present contribution aims to provide a motivational perspective on eating regulation. The role of satisfaction and thwarting of the basic psychological needs for autonomy, competence, and relatedness is introduced as a mechanism to (a) explain the etiology of body image concerns and disordered eating and (b) understand the optimal regulation of ongoing eating behavior for healthy weight maintenance. An overview of empirical studies on these two research lines is provided. In a final section, the potential relevance and value of SDT in relation to prevailing theoretical models in the domain of eating regulation is discussed. Although research on SDT in the domain of eating regulation is still in its early stages and more research is clearly needed, this review suggests that the SDT represents a promising framework to more thoroughly study and understand the motivational processes involved in eating regulation and associated problems. PMID:22385782

  14. Motivational dynamics of eating regulation: a self-determination theory perspective

    Directory of Open Access Journals (Sweden)

    Verstuyf Joke

    2012-03-01

    Full Text Available Abstract Within Western society, many people have difficulties adequately regulating their eating behaviors and weight. Although the literature on eating regulation is vast, little attention has been given to motivational dynamics involved in eating regulation. Grounded in Self-Determination Theory (SDT, the present contribution aims to provide a motivational perspective on eating regulation. The role of satisfaction and thwarting of the basic psychological needs for autonomy, competence, and relatedness is introduced as a mechanism to (a explain the etiology of body image concerns and disordered eating and (b understand the optimal regulation of ongoing eating behavior for healthy weight maintenance. An overview of empirical studies on these two research lines is provided. In a final section, the potential relevance and value of SDT in relation to prevailing theoretical models in the domain of eating regulation is discussed. Although research on SDT in the domain of eating regulation is still in its early stages and more research is clearly needed, this review suggests that the SDT represents a promising framework to more thoroughly study and understand the motivational processes involved in eating regulation and associated problems.

  15. Dynamic studies of multiple configurations of CERN's Antiproton Decelerator Target core under proton beam impact

    CERN Document Server

    AUTHOR|(CDS)2248381

    Antiprotons, like many other exotic particles, are produced by impacting high energy proton beams onto fixed targets. At the European Organization for Nuclear Research (CERN), this is done in the Antiproton Decelerator (AD) Facility. The engineering challenges related to the design of an optimal configuration of the AD-Target system derive from the extremely high energy depositions reached in the very thin target core as a consequence of each proton beam impact. A new target design is foreseen for operation after 2021, triggering multiple R&D activities since 2013 for this purpose. The goal of the present Master Thesis is to complement these activities with analytical and numerical calculations, delving into the phenomena associated to the dynamic response of the target core. In this context, two main studies have been carried out. First, the experimental data observed in targets subjected to low intensity proton pulses was cross-checked with analytical and computational methods for modal analysis, applie...

  16. Solving the Single-Sink, Fixed-Charge, Multiple-Choice Transportation Problem by Dynamic Programming

    DEFF Research Database (Denmark)

    Rauff Lind Christensen, Tue; Klose, Andreas; Andersen, Kim Allan

    The Single-Sink, Fixed-Charge, Multiple-Choice Transportation Problem (SSFCMCTP) is a problem with versatile applications. This problem is a generalization of the Single-Sink, Fixed-Charge Transportation Problem (SSFCTP), which has a fixed-charge, linear cost structure. However, in at least two...... are neglected in the SSFCTP. The SSFCMCTP overcome this problem by incorporating a staircase cost structure in the cost function instead of the usual one used in SSFCTP. We present a dynamic programming algorithm for the resulting problem. To enhance the performance of the generic algorithm a number...... of enhancements is employed. The problem instance is reduced by variable pegging using a Lagrangean relaxation from which also a flow augmentation scheme is derived. Additionally a reduction in the search space is employed along with a variable transformation which generalizes a transformation known from...

  17. Global Software Development: Exploring Multiplicity and Asymmetric Dynamics in Collaborative Work

    DEFF Research Database (Denmark)

    Matthiesen, Stina

    This overview presents the mid stages of my doctoral research—based on ethnographic work conducted in IT companies in India and in Denmark—on collaborative work within global software development (GSD). In the following I briefly introduce how this research seeks to spark a debate in CSCW by chal...... by challenging contemporary ideals about software development outsourcing through the exploration of the multiplicities and asymmetric dynamics inherent in the collaborative work of GSD.......This overview presents the mid stages of my doctoral research—based on ethnographic work conducted in IT companies in India and in Denmark—on collaborative work within global software development (GSD). In the following I briefly introduce how this research seeks to spark a debate in CSCW...

  18. Radiosurgery of multiple brain metastases with single-isocenter dynamic conformal arcs (SIDCA)

    International Nuclear Information System (INIS)

    Huang, Yimei; Chin, Karen; Robbins, Jared R.; Kim, Jinkoo; Li, Haisen; Amro, Hanan; Chetty, Indrin J.; Gordon, James; Ryu, Samuel

    2014-01-01

    Purpose: To propose single-isocenter dynamic conformal arcs (SIDCA), a novel technique for radiosurgery of multiple brain metastases, and to compare SIDCA with volumetric modulated arc therapy (VMAT) and multiple-isocenter dynamic conformal arcs (MIDCA) for plan quality. Methods and materials: SIDCA, MIDCA, and VMAT plans were created on 6 patients with 3–5 metastases. Plans were evaluated using Radiation Therapy Oncology Group conformity index (RCI), Paddick conformity index (PCI), gradient index (GI), volumes that received more than 100% (V 100% ), 50% (V 50% ), 25% (V 25% ) and 10% (V 10% ) of prescription dose, total monitor units (MUs), and delivery time (DT). Results: SIDCA achieved conformal plans (RCI = 1.38 ± 0.12, PCI = 0.72 ± 0.06) with steep dose fall-off (GI = 3.97 ± 0.51). MIDCA plans had comparable plan quality and MUs as SIDCA, but 52% longer DT. The VMAT plans had better conformity (RCI = 1.15 ± 0.09, p < 0.01 and PCI = 0.86 ± 0.06, p < 0.01) than SIDCA, worse GI (4.34 ± 0.46, p < 0.01), higher V 25% (p = 0.05) and V 10% (p = 0.02), 49% less MUs and 46% shorter DT. Conclusions: All three techniques achieved conformal plans with steep dose fall-off from targets. SIDCA plans had similar plan quality as MIDCA but more efficient to delivery. SIDCA plans had lower peripheral dose spread than VMAT; VMAT plans had better conformity and faster delivery time than SIDCA

  19. The Prolactin Gene: A Paradigm of Tissue-Specific Gene Regulation with Complex Temporal Transcription Dynamics

    Science.gov (United States)

    Featherstone, K; White, M R H; Davis, J R E

    2012-01-01

    Transcription of numerous mammalian genes is highly pulsatile, with bursts of expression occurring with variable duration and frequency. The presence of this stochastic or ‘noisy’ expression pattern has been relatively unexplored in tissue systems. The prolactin gene provides a model of tissue-specific gene regulation resulting in pulsatile transcription dynamics in both cell lines and endocrine tissues. In most cell culture models, prolactin transcription appears to be highly variable between cells, with differences in transcription pulse duration and frequency. This apparently stochastic transcription is constrained by a transcriptional refractory period, which may be related to cycles of chromatin remodelling. We propose that prolactin transcription dynamics result from the summation of oscillatory cellular inputs and by regulation through chromatin remodelling cycles. Observations of transcription dynamics in cells within pituitary tissue show reduced transcriptional heterogeneity and can be grouped into a small number of distinct patterns. Thus, it appears that the tissue environment is able to reduce transcriptional noise to enable coordinated tissue responses to environmental change. We review the current knowledge on the complex tissue-specific regulation of the prolactin gene in pituitary and extra-pituitary sites, highlighting differences between humans and rodent experimental animal models. Within this context, we describe the transcription dynamics of prolactin gene expression and how this may relate to specific processes occurring within the cell. PMID:22420298

  20. JMJD1C Exhibits Multiple Functions in Epigenetic Regulation during Spermatogenesis.

    Directory of Open Access Journals (Sweden)

    Ryusuke Nakajima

    Full Text Available Jmjd1C is one of the Jmjd1 family genes that encode putative demethylases against histone H3K9 and non-histone proteins and has been proven to play an indispensable role in mouse spermatogenesis. Here, we analyzed a newly-bred transgenic mouse strain carrying a Jmjd1C loss-of-function allele in which a β-geo cassette was integrated into the intron of the Jmjd1C locus. Jmjd1C gene-trap homozygous testes exhibited malformations in postmeiotic processes and a deficiency in the long-term maintenance of undifferentiated spermatogonia. Some groups of spermatids in the homozygous testis showed abnormal organization and incomplete elongation from the first wave of spermatogenesis onwards. Moreover, histone H4K16 acetylation, which is required for the onset of chromatin remodeling, appeared to be remarkably decreased. These effects may not have been a result of the drastic decrease in gene expression related to the events but instead may have been due to the lack of interaction between JMJD1C and its partner proteins, such as MDC1 and HSP90. Additionally, significant decreases in Oct4 expression and NANOG- and OCT4-expressing spermatogonia were found in the Jmjd1C homozygous mature testis, suggesting that JMJD1C may participate in the maintenance of spermatogonial stem cell self-renewal by up-regulating Oct4 expression. These results indicate that JMJD1C has multiple functions during spermatogenesis through interactions with different partners during the spermatogenic stages.

  1. Multiple markers for melanoma progression regulated by DNA methylation: insights from transcriptomic studies.

    Science.gov (United States)

    Gallagher, William M; Bergin, Orla E; Rafferty, Mairin; Kelly, Zoë D; Nolan, Ilse-Maria; Fox, Edward J P; Culhane, Aedin C; McArdle, Linda; Fraga, Mario F; Hughes, Linda; Currid, Caroline A; O'Mahony, Fiona; Byrne, Aileen; Murphy, Alison A; Moss, Catherine; McDonnell, Susan; Stallings, Raymond L; Plumb, Jane A; Esteller, Manel; Brown, Robert; Dervan, Peter A; Easty, David J

    2005-11-01

    The incidence of melanoma is increasing rapidly, with advanced lesions generally failing to respond to conventional chemotherapy. Here, we utilized DNA microarray-based gene expression profiling techniques to identify molecular determinants of melanoma progression within a unique panel of isogenic human melanoma cell lines. When a poorly tumorigenic cell line, derived from an early melanoma, was compared with two increasingly aggressive derivative cell lines, the expression of 66 genes was significantly changed. A similar pattern of differential gene expression was found with an independently derived metastatic cell line. We further examined these melanoma progression-associated genes via use of a tailored TaqMan Low Density Array (LDA), representing the majority of genes within our cohort of interest. Considerable concordance was seen between the transcriptomic profiles determined by DNA microarray and TaqMan LDA approaches. A range of novel markers were identified that correlated here with melanoma progression. Most notable was TSPY, a Y chromosome-specific gene that displayed extensive down-regulation in expression between the parental and derivative cell lines. Examination of a putative CpG island within the TSPY gene demonstrated that this region was hypermethylated in the derivative cell lines, as well as metastatic melanomas from male patients. Moreover, treatment of the derivative cell lines with the DNA methyltransferase inhibitor, 2'-deoxy-5-azacytidine (DAC), restored expression of the TSPY gene to levels comparable with that found in the parental cells. Additional DNA microarray studies uncovered a subset of 13 genes from the above-mentioned 66 gene cohort that displayed re-activation of expression following DAC treatment, including TSPY, CYBA and MT2A. DAC suppressed tumor cell growth in vitro. Moreover, systemic treatment of mice with DAC attenuated growth of melanoma xenografts, with consequent re-expression of TSPY mRNA. Overall, our data support

  2. Mitochondrial Dynamics Impacts Stem Cell Identity and Fate Decisions by Regulating a Nuclear Transcriptional Program.

    Science.gov (United States)

    Khacho, Mireille; Clark, Alysen; Svoboda, Devon S; Azzi, Joelle; MacLaurin, Jason G; Meghaizel, Cynthia; Sesaki, Hiromi; Lagace, Diane C; Germain, Marc; Harper, Mary-Ellen; Park, David S; Slack, Ruth S

    2016-08-04

    Regulated mechanisms of stem cell maintenance are key to preventing stem cell depletion and aging. While mitochondrial morphology plays a fundamental role in tissue development and homeostasis, its role in stem cells remains unknown. Here, we uncover that mitochondrial dynamics regulates stem cell identity, self-renewal, and fate decisions by orchestrating a transcriptional program. Manipulation of mitochondrial structure, through OPA1 or MFN1/2 deletion, impaired neural stem cell (NSC) self-renewal, with consequent age-dependent depletion, neurogenesis defects, and cognitive impairments. Gene expression profiling revealed ectopic expression of the Notch self-renewal inhibitor Botch and premature induction of transcription factors that promote differentiation. Changes in mitochondrial dynamics regulate stem cell fate decisions by driving a physiological reactive oxygen species (ROS)-mediated process, which triggers a dual program to suppress self-renewal and promote differentiation via NRF2-mediated retrograde signaling. These findings reveal mitochondrial dynamics as an upstream regulator of essential mechanisms governing stem cell self-renewal and fate decisions through transcriptional programming. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Dynamics of chromatin accessibility and gene regulation by MADS-domain transcription factors in flower development.

    Science.gov (United States)

    Pajoro, Alice; Madrigal, Pedro; Muiño, Jose M; Matus, José Tomás; Jin, Jian; Mecchia, Martin A; Debernardi, Juan M; Palatnik, Javier F; Balazadeh, Salma; Arif, Muhammad; Ó'Maoiléidigh, Diarmuid S; Wellmer, Frank; Krajewski, Pawel; Riechmann, José-Luis; Angenent, Gerco C; Kaufmann, Kerstin

    2014-03-03

    Development of eukaryotic organisms is controlled by transcription factors that trigger specific and global changes in gene expression programs. In plants, MADS-domain transcription factors act as master regulators of developmental switches and organ specification. However, the mechanisms by which these factors dynamically regulate the expression of their target genes at different developmental stages are still poorly understood. We characterized the relationship of chromatin accessibility, gene expression, and DNA binding of two MADS-domain proteins at different stages of Arabidopsis flower development. Dynamic changes in APETALA1 and SEPALLATA3 DNA binding correlated with changes in gene expression, and many of the target genes could be associated with the developmental stage in which they are transcriptionally controlled. We also observe dynamic changes in chromatin accessibility during flower development. Remarkably, DNA binding of APETALA1 and SEPALLATA3 is largely independent of the accessibility status of their binding regions and it can precede increases in DNA accessibility. These results suggest that APETALA1 and SEPALLATA3 may modulate chromatin accessibility, thereby facilitating access of other transcriptional regulators to their target genes. Our findings indicate that different homeotic factors regulate partly overlapping, yet also distinctive sets of target genes in a partly stage-specific fashion. By combining the information from DNA-binding and gene expression data, we are able to propose models of stage-specific regulatory interactions, thereby addressing dynamics of regulatory networks throughout flower development. Furthermore, MADS-domain TFs may regulate gene expression by alternative strategies, one of which is modulation of chromatin accessibility.

  4. Disordered and Multiple Destinations Path Planning Methods for Mobile Robot in Dynamic Environment

    Directory of Open Access Journals (Sweden)

    Yong-feng Dong

    2016-01-01

    Full Text Available In the smart home environment, aiming at the disordered and multiple destinations path planning, the sequencing rule is proposed to determine the order of destinations. Within each branching process, the initial feasible path set is generated according to the law of attractive destination. A sinusoidal adaptive genetic algorithm is adopted. It can calculate the crossover probability and mutation probability adaptively changing with environment at any time. According to the cultural-genetic algorithm, it introduces the concept of reducing turns by parallelogram and reducing length by triangle in the belief space, which can improve the quality of population. And the fallback strategy can help to jump out of the “U” trap effectively. The algorithm analyses the virtual collision in dynamic environment with obstacles. According to the different collision types, different strategies are executed to avoid obstacles. The experimental results show that cultural-genetic algorithm can overcome the problems of premature and convergence of original algorithm effectively. It can avoid getting into the local optimum. And it is more effective for mobile robot path planning. Even in complex environment with static and dynamic obstacles, it can avoid collision safely and plan an optimal path rapidly at the same time.

  5. Construction of multiple trade-offs to obtain arbitrary singularities of adaptive dynamics.

    Science.gov (United States)

    Kisdi, Éva

    2015-04-01

    Evolutionary singularities are central to the adaptive dynamics of evolving traits. The evolutionary singularities are strongly affected by the shape of any trade-off functions a model assumes, yet the trade-off functions are often chosen in an ad hoc manner, which may unjustifiably constrain the evolutionary dynamics exhibited by the model. To avoid this problem, critical function analysis has been used to find a trade-off function that yields a certain evolutionary singularity such as an evolutionary branching point. Here I extend this method to multiple trade-offs parameterized with a scalar strategy. I show that the trade-off functions can be chosen such that an arbitrary point in the viability domain of the trait space is a singularity of an arbitrary type, provided (next to certain non-degeneracy conditions) that the model has at least two environmental feedback variables and at least as many trade-offs as feedback variables. The proof is constructive, i.e., it provides an algorithm to find trade-off functions that yield the desired singularity. I illustrate the construction of trade-offs with an example where the virulence of a pathogen evolves in a small ecosystem of a host, its pathogen, a predator that attacks the host and an alternative prey of the predator.

  6. Use of multiple CT scans to accommodate large objects and stretch dynamic range of detectability

    Energy Technology Data Exchange (ETDEWEB)

    Sivers, E.A.

    1994-09-01

    Rotate-only X-ray CT scanners are preferred for their speed and dose utilization, but suffer from the restriction that the scanned object must fit within the radiation beam. In addition, the ratio of signals unattenuated by air paths to those penetrating thick, dense objects often exceeds the dynamic range of conventional X-ray detectors. Both of these disadvantages can be removed for objects larger than the X-ray beam by taking multiple scans, each of which exposes only part of the object. These partial data sets can then be merged to produce a complete data set. For most objects, it is also possible to separately expose regions in which the ratios between the extremes of attenuation are much lower than that between air and the maximum path length. It is therefore possible to use a higher flux to image denser regions, improving signal-to-noise ratios and yielding images superior to those of larger scanners having the same dynamic range,

  7. The impact of multiple noise sources on maximally informative adaptive dynamics in neural populations

    Science.gov (United States)

    Hsu, Wei-Mien Mendy; Kastner, David; Baccus, Stephen; Sharpee, Tatyana

    Sensory neural populations are thought to be optimized to transmit information about the sensory environment either in the course of evolution in the dynamically to adapt neural responses to the current stimulus environment. Recent work has shown that when encoding a particular stimulus feature, the existence of multiple neuronal types with different thresholds increases information transmission when sensory noise drops below a certain level. This prediction across an evolutionary timescale simultaneously explains the existence of adapting and sensitizing Off retinal ganglion cells, which have high and low thresholds for spiking, respectively, as well as the absence of comparable types among On that have higher effective noise level. However, the difference in thresholds between adapting and sensitizing cells is systematically lower than the one that would yield maximal information in an environment of stationary contrast. Here we show how predictions for the optimal threshold difference change when the overall sensory noise is treated as the combination of multiple noise sources separated by nonlinear steps. Analyzing responses of adapting and sensitizing ganglion cells types we identify an additional noise source that affects adapting but not sensitizing ganglion cells. NSF CAREER Award IIS-1254123, NSF IOS-1556388 (T.O.S.); 2016 Salk Women & Science Special Award (W.M.H); NEI Grant (S.A.B.).

  8. [Dynamic accumulation regulation of curcumin, demethoxycurcumin and bisdemethoxyeurcumin in three strains of curcuma longae rhizome].

    Science.gov (United States)

    Li, Qing-Miao; Yang, Wen-Yu; Tang, Xue-Mei; Zhang, Mei; Zhou, Xian-Jian; Shu, Guang-Ming; Zhao, Jun-Ning; Fang, Qing-Mao

    2014-06-01

    The paper is aimed to study the dynamic accumulation regulation of curcumin (Cur), demethoxycurcumin (DMC) and bisdemethoxyeurcumin (BDMC) in three strains of Curcuma longa, and provide scientific references for formalized cultivation, timely harvesting, quality control and breeding cultivation of C. longa. The accumulation regulation of the three curcumin derivatives was basically the same in rhizome of three strains. The relative contents decreased along with plant development growing, while the accumulation per hectare increased with plant development growing. The accumulation of curcuminoids per hectare could be taken as the assessment standard for the best harvest time of C. longa. A3 was the best strain in terms of Cur and BDMC content.

  9. Behavior control in the sensorimotor loop with short-term synaptic dynamics induced by self-regulating neurons

    Directory of Open Access Journals (Sweden)

    Hazem eToutounji

    2014-05-01

    Full Text Available The behavior and skills of living systems depend on the distributed control provided by specialized and highly recurrent neural networks. Learning and memory in these systems is mediated by a set of adaptation mechanisms, known collectively as neuronal plasticity. Translating principles of recurrent neural control and plasticity to artificial agents has seen major strides, but is usually hampered by the complex interactions between the agent's body and its environment. One of the important standing issues is for the agent to support multiple stable states of behavior, so that its behavioral repertoire matches the requirements imposed by these interactions. The agent also must have the capacity to switch between these states in time scales that are comparable to those by which sensory stimulation varies. Achieving this requires a mechanism of short-term memory that allows the neurocontroller to keep track of the recent history of its input, which finds its biological counterpart in short-term synaptic plasticity. This issue is approached here by deriving synaptic dynamics in recurrent neural networks. Neurons are introduced as self-regulating units with a rich repertoire of dynamics. They exhibit homeostatic properties for certain parameter domains, which result in a set of stable states and the required short-term memory. They can also operate as oscillators, which allow them to surpass the level of activity imposed by their homeostatic operation conditions. Neural systems endowed with the derived synaptic dynamics can be utilized for the neural behavior control of autonomous mobile agents. The resulting behavior depends also on the underlying network structure, which is either engineered, or developed by evolutionary techniques. The effectiveness of these self-regulating units is demonstrated by controlling locomotion of a hexapod with eighteen degrees of freedom, and obstacle-avoidance of a wheel-driven robot.

  10. Comparing cluster-level dynamic treatment regimens using sequential, multiple assignment, randomized trials: Regression estimation and sample size considerations.

    Science.gov (United States)

    NeCamp, Timothy; Kilbourne, Amy; Almirall, Daniel

    2017-08-01

    Cluster-level dynamic treatment regimens can be used to guide sequential treatment decision-making at the cluster level in order to improve outcomes at the individual or patient-level. In a cluster-level dynamic treatment regimen, the treatment is potentially adapted and re-adapted over time based on changes in the cluster that could be impacted by prior intervention, including aggregate measures of the individuals or patients that compose it. Cluster-randomized sequential multiple assignment randomized trials can be used to answer multiple open questions preventing scientists from developing high-quality cluster-level dynamic treatment regimens. In a cluster-randomized sequential multiple assignment randomized trial, sequential randomizations occur at the cluster level and outcomes are observed at the individual level. This manuscript makes two contributions to the design and analysis of cluster-randomized sequential multiple assignment randomized trials. First, a weighted least squares regression approach is proposed for comparing the mean of a patient-level outcome between the cluster-level dynamic treatment regimens embedded in a sequential multiple assignment randomized trial. The regression approach facilitates the use of baseline covariates which is often critical in the analysis of cluster-level trials. Second, sample size calculators are derived for two common cluster-randomized sequential multiple assignment randomized trial designs for use when the primary aim is a between-dynamic treatment regimen comparison of the mean of a continuous patient-level outcome. The methods are motivated by the Adaptive Implementation of Effective Programs Trial which is, to our knowledge, the first-ever cluster-randomized sequential multiple assignment randomized trial in psychiatry.

  11. Direct evaluation of boson dynamics via finite-temperature time-dependent variation with multiple Davydov states

    Science.gov (United States)

    Fujihashi, Yuta; Wang, Lu; Zhao, Yang

    2017-12-01

    Recent advances in quantum optics allow for exploration of boson dynamics in dissipative many-body systems. However, the traditional descriptions of quantum dissipation using reduced density matrices are unable to capture explicit information of bath dynamics. In this work, efficient evaluation of boson dynamics is demonstrated by combining the multiple Davydov Ansatz with finite-temperature time-dependent variation, going beyond what state-of-the-art density matrix approaches are capable to offer for coupled electron-boson systems. To this end, applications are made to excitation energy transfer in photosynthetic systems, singlet fission in organic thin films, and circuit quantum electrodynamics in superconducting devices. Thanks to the multiple Davydov Ansatz, our analysis of boson dynamics leads to clear revelation of boson modes strongly coupled to electronic states, as well as in-depth description of polaron creation and destruction in the presence of thermal fluctuations.

  12. Effects of automobile steering characteristics on driver vehicle system dynamics in regulation tasks

    Science.gov (United States)

    Mcruer, D. T.; Klein, R.

    1975-01-01

    A regulation task which subjected the automobile to a random gust disturbance which is countered by driver control action is used to study the effects of various automobile steering characteristics on the driver/vehicle system. The experiments used a variable stability automobile specially configured to permit insertion of the simulated gust disturbance and the measurement of the driver/vehicle system characteristics. Driver/vehicle system dynamics were measured and interpreted as an effective open loop system describing function. Objective measures of system bandwidth, stability, and time delays were deduced and compared. These objective measures were supplemented by driver ratings. A tentative optimum range of vehicle dynamics for the directional regulation task was established.

  13. ABBA regulates plasma-membrane and actin dynamics to promote radial glia extension.

    Science.gov (United States)

    Saarikangas, Juha; Hakanen, Janne; Mattila, Pieta K; Grumet, Martin; Salminen, Marjo; Lappalainen, Pekka

    2008-05-01

    Radial glia play key roles in neuronal migration, axon guidance, and neurogenesis during development of the central nervous system. However, the molecular mechanisms regulating growth and morphology of these extended cells are unknown. We show that ABBA, a novel member of the IRSp53-MIM protein family, is enriched in different types of radial glia. ABBA binds ATP-actin monomers with high affinity and deforms PtdIns(4,5)P(2)-rich membranes in vitro through its WH2 and IM domains, respectively. In radial-glia-like C6-R cells, ABBA localises to the interface between the actin cytoskeleton and plasma membrane, and its depletion by RNAi led to defects in lamellipodial dynamics and process extension. Together, this study identifies ABBA as a novel regulator of actin and plasma membrane dynamics in radial glial cells, and provides evidence that membrane binding and deformation activity is critical for the cellular functions of IRSp53-MIM-ABBA family proteins.

  14. Dynamic Transcriptional Regulation of Fis in Salmonella During the Exponential Phase.

    Science.gov (United States)

    Wang, Hui; Wang, Lei; Li, Ping; Hu, Yilang; Zhang, Wei; Tang, Bo

    2015-12-01

    Fis is one of the most important global regulators and has attracted extensive research attention. Many studies have focused on comparing the Fis global regulatory networks for exploring Fis function during different growth stages, such as the exponential and stationary stages. Although the Fis protein in bacteria is mainly expressed in the exponential phase, the dynamic transcriptional regulation of Fis during the exponential phase remains poorly understood. To address this question, we used RNA-seq technology to identify the Fis-regulated genes in the S. enterica serovar Typhimurium during the early exponential phase, and qRT-PCR was performed to validate the transcriptional data. A total of 1495 Fis-regulated genes were successfully identified, including 987 Fis-repressed genes and 508 Fis-activated genes. Comparing the results of this study with those of our previous study, we found that the transcriptional regulation of Fis was diverse during the early- and mid-exponential phases. The results also showed that the strong positive regulation of Fis on Salmonella pathogenicity island genes in the mid-exponential phase transitioned into insignificant effect in the early exponential phase. To validate these results, we performed a cell infection assay and found that Δfis only exhibited a 1.49-fold decreased capacity compared with the LT2 wild-type strain, indicating a large difference from the 6.31-fold decrease observed in the mid-exponential phase. Our results provide strong evidence for a need to thoroughly understand the dynamic transcriptional regulation of Fis in Salmonella during the exponential phase.

  15. Rigid-flexible coupling dynamic modeling and investigation of a redundantly actuated parallel manipulator with multiple actuation modes

    Science.gov (United States)

    Liang, Dong; Song, Yimin; Sun, Tao; Jin, Xueying

    2017-09-01

    A systematic dynamic modeling methodology is presented to develop the rigid-flexible coupling dynamic model (RFDM) of an emerging flexible parallel manipulator with multiple actuation modes. By virtue of assumed mode method, the general dynamic model of an arbitrary flexible body with any number of lumped parameters is derived in an explicit closed form, which possesses the modular characteristic. Then the completely dynamic model of system is formulated based on the flexible multi-body dynamics (FMD) theory and the augmented Lagrangian multipliers method. An approach of combining the Udwadia-Kalaba formulation with the hybrid TR-BDF2 numerical algorithm is proposed to address the nonlinear RFDM. Two simulation cases are performed to investigate the dynamic performance of the manipulator with different actuation modes. The results indicate that the redundant actuation modes can effectively attenuate vibration and guarantee higher dynamic performance compared to the traditional non-redundant actuation modes. Finally, a virtual prototype model is developed to demonstrate the validity of the presented RFDM. The systematic methodology proposed in this study can be conveniently extended for the dynamic modeling and controller design of other planar flexible parallel manipulators, especially the emerging ones with multiple actuation modes.

  16. Features of Autonomic Regulation of Cardiorespiration System in Dynamics of Training Cycle of Year

    OpenAIRE

    Romanchuk, A.P.

    2015-01-01

    In the given work the analysis of the results of the research of the vegetative regulation of cardiorespiration system with the help of spiroarterio- cardiorythmography is carried out in dynamics of a training cycle of a year. According to the change of the parameters of ratio LF/HF of variability of a cardiac rhythm, systolic and diastolic arterial pressure, and also spontaneous respiration, the analysis is carried out for ranking distributions and correlation matrixes which has allowed to d...

  17. Digitalising the General Data Protection Regulation with Dynamic Condition Response Graphs

    DEFF Research Database (Denmark)

    Heuck, Emil; Hildebrandt, Thomas; Kiærulff Lerche, Rasmus

    2017-01-01

    We describe how the declarative Dynamic Condition Response (DCR) Graphs proces notation can be used to digitalise the General Data Protection Regulation (GDPR) and make a first evaluation to what extend the formalisation and associated tool for end-user modelling and simulation can be used...... to clarify the meaning of the GDPR and its consequences for the main business process of a Danish funding agency....

  18. A regulation probability model-based meta-analysis of multiple transcriptomics data sets for cancer biomarker identification.

    Science.gov (United States)

    Xie, Xin-Ping; Xie, Yu-Feng; Wang, Hong-Qiang

    2017-08-23

    Large-scale accumulation of omics data poses a pressing challenge of integrative analysis of multiple data sets in bioinformatics. An open question of such integrative analysis is how to pinpoint consistent but subtle gene activity patterns across studies. Study heterogeneity needs to be addressed carefully for this goal. This paper proposes a regulation probability model-based meta-analysis, jGRP, for identifying differentially expressed genes (DEGs). The method integrates multiple transcriptomics data sets in a gene regulatory space instead of in a gene expression space, which makes it easy to capture and manage data heterogeneity across studies from different laboratories or platforms. Specifically, we transform gene expression profiles into a united gene regulation profile across studies by mathematically defining two gene regulation events between two conditions and estimating their occurring probabilities in a sample. Finally, a novel differential expression statistic is established based on the gene regulation profiles, realizing accurate and flexible identification of DEGs in gene regulation space. We evaluated the proposed method on simulation data and real-world cancer datasets and showed the effectiveness and efficiency of jGRP in identifying DEGs identification in the context of meta-analysis. Data heterogeneity largely influences the performance of meta-analysis of DEGs identification. Existing different meta-analysis methods were revealed to exhibit very different degrees of sensitivity to study heterogeneity. The proposed method, jGRP, can be a standalone tool due to its united framework and controllable way to deal with study heterogeneity.

  19. Probing molecular mechanisms of the Hsp90 chaperone: biophysical modeling identifies key regulators of functional dynamics.

    Science.gov (United States)

    Dixit, Anshuman; Verkhivker, Gennady M

    2012-01-01

    Deciphering functional mechanisms of the Hsp90 chaperone machinery is an important objective in cancer biology aiming to facilitate discovery of targeted anti-cancer therapies. Despite significant advances in understanding structure and function of molecular chaperones, organizing molecular principles that control the relationship between conformational diversity and functional mechanisms of the Hsp90 activity lack a sufficient quantitative characterization. We combined molecular dynamics simulations, principal component analysis, the energy landscape model and structure-functional analysis of Hsp90 regulatory interactions to systematically investigate functional dynamics of the molecular chaperone. This approach has identified a network of conserved regions common to the Hsp90 chaperones that could play a universal role in coordinating functional dynamics, principal collective motions and allosteric signaling of Hsp90. We have found that these functional motifs may be utilized by the molecular chaperone machinery to act collectively as central regulators of Hsp90 dynamics and activity, including the inter-domain communications, control of ATP hydrolysis, and protein client binding. These findings have provided support to a long-standing assertion that allosteric regulation and catalysis may have emerged via common evolutionary routes. The interaction networks regulating functional motions of Hsp90 may be determined by the inherent structural architecture of the molecular chaperone. At the same time, the thermodynamics-based "conformational selection" of functional states is likely to be activated based on the nature of the binding partner. This mechanistic model of Hsp90 dynamics and function is consistent with the notion that allosteric networks orchestrating cooperative protein motions can be formed by evolutionary conserved and sparsely connected residue clusters. Hence, allosteric signaling through a small network of distantly connected residue clusters may be

  20. Probing molecular mechanisms of the Hsp90 chaperone: biophysical modeling identifies key regulators of functional dynamics.

    Directory of Open Access Journals (Sweden)

    Anshuman Dixit

    Full Text Available Deciphering functional mechanisms of the Hsp90 chaperone machinery is an important objective in cancer biology aiming to facilitate discovery of targeted anti-cancer therapies. Despite significant advances in understanding structure and function of molecular chaperones, organizing molecular principles that control the relationship between conformational diversity and functional mechanisms of the Hsp90 activity lack a sufficient quantitative characterization. We combined molecular dynamics simulations, principal component analysis, the energy landscape model and structure-functional analysis of Hsp90 regulatory interactions to systematically investigate functional dynamics of the molecular chaperone. This approach has identified a network of conserved regions common to the Hsp90 chaperones that could play a universal role in coordinating functional dynamics, principal collective motions and allosteric signaling of Hsp90. We have found that these functional motifs may be utilized by the molecular chaperone machinery to act collectively as central regulators of Hsp90 dynamics and activity, including the inter-domain communications, control of ATP hydrolysis, and protein client binding. These findings have provided support to a long-standing assertion that allosteric regulation and catalysis may have emerged via common evolutionary routes. The interaction networks regulating functional motions of Hsp90 may be determined by the inherent structural architecture of the molecular chaperone. At the same time, the thermodynamics-based "conformational selection" of functional states is likely to be activated based on the nature of the binding partner. This mechanistic model of Hsp90 dynamics and function is consistent with the notion that allosteric networks orchestrating cooperative protein motions can be formed by evolutionary conserved and sparsely connected residue clusters. Hence, allosteric signaling through a small network of distantly connected

  1. An experimental investigation of a liquid cooling scheme for the low dropout voltage regulators of the multiplicity and vertex detector

    International Nuclear Information System (INIS)

    Bernardin, J.D.; Bosze, E.

    1997-10-01

    This report presents a summary of an experimental investigation of a liquid cooling system for the low dropout voltage regulators in the multiplicity and vertex detector (MVD), a device used to determine and characterize the collision location of two accelerated heavy ions. The coolant temperatures and flow rates as well as the voltage regulator operating temperatures were used to assess and optimize the performance of the proposed cooling system, identify potential assembly problems and system limitations, and provide the necessary information for designing and sizing the final MVD cooling system components. The MVD is part of the PHENIX experiment at Brookhaven RHIC

  2. The Kinesin Adaptor Calsyntenin-1 Organizes Microtubule Polarity and Regulates Dynamics during Sensory Axon Arbor Development

    Directory of Open Access Journals (Sweden)

    Mary C. Halloran

    2017-04-01

    Full Text Available Axon growth and branching, and development of neuronal polarity are critically dependent on proper organization and dynamics of the microtubule (MT cytoskeleton. MTs must organize with correct polarity for delivery of diverse cargos to appropriate subcellular locations, yet the molecular mechanisms regulating MT polarity remain poorly understood. Moreover, how an actively branching axon reorganizes MTs to direct their plus ends distally at branch points is unknown. We used high-speed, in vivo imaging of polymerizing MT plus ends to characterize MT dynamics in developing sensory axon arbors in zebrafish embryos. We find that axonal MTs are highly dynamic throughout development, and that the peripheral and central axons of sensory neurons show differences in MT behaviors. Furthermore, we show that Calsyntenin-1 (Clstn-1, a kinesin adaptor required for sensory axon branching, also regulates MT polarity in developing axon arbors. In wild type neurons the vast majority of MTs are directed in the correct plus-end-distal orientation from early stages of development. Loss of Clstn-1 causes an increase in MTs polymerizing in the retrograde direction. These misoriented MTs most often are found near growth cones and branch points, suggesting Clstn-1 is particularly important for organizing MT polarity at these locations. Together, our results suggest that Clstn-1, in addition to regulating kinesin-mediated cargo transport, also organizes the underlying MT highway during axon arbor development.

  3. A dynamic model for firm-response to non-credible incentive regulation regimes

    International Nuclear Information System (INIS)

    Agrell, Per J.; Grifell-Tatjé, Emili

    2016-01-01

    Economic network regulation increasingly use quantitative performance models (from econometrics and engineering) to set revenues. In theory, high-powered incentive regulation, such as revenue-caps, induces firms to cost-efficient behavior independent of underlying model. However, anecdotal evidence shows regulated firms occasionally maintaining cost-inefficiency under incentive regulation even under slumping profitability. We present a model for firm-level efficiency under a regime with a probability of failure explaining this phenomenon. The model is based on the hypothesis that the regulatory choice of method can be associated with intrinsic flaws leading to judicial repeal and replacement of it by a low-powered regime. The results show that the cost efficiency policy is proportional to the type of firm (cost of effort), value of time (discount factor) and the credibility of the method (risk of failure). A panel data set for 2000–2006 for 128 electricity distributors in Sweden is used to validate the model predictions (radical productivity slowdown, failing profitability and efficiency) at the launch and demise of a non-credible regulation method. The work highlights the fallacy of viewing incentive regulation as a method-independent instrument, a result applicable in any infrastructure regulation. - Highlights: • Incentive regulation relies on fixed revenue for operators. • In existing theory the efficiency-inducing effect is model-independent. • A dynamic game exposes the firm to a regulation that may fail. • One optimal policy is to pad cost and wait for the failure. • The Swedish DSOs show this policy 2003–2006, when the regime failed.

  4. Dynamic regulation of NMDAR function in the adult brain by the stress hormone corticosterone

    Directory of Open Access Journals (Sweden)

    Yiu Chung eTse

    2012-03-01

    Full Text Available Stress and corticosteroids dynamically modulate the expression of synaptic plasticity at glutamatergic synapses in the developed brain. Together with alpha-amino-3-hydroxy-methyl-4-isoxazole propionic acid receptors (AMPAR, N-methyl-D-aspartate receptors (NMDAR are critical mediators of synaptic function and are essential for the induction of many forms of synaptic plasticity. Regulation of NMDAR function by cortisol/corticosterone (CORT may be fundamental to the effects of stress on synaptic plasticity. Recent reports of the efficacy of NMDAR antagonists in treating certain stress-associated psychopathologies further highlight the importance of understanding the regulation of NMDAR function by CORT. Knowledge of how corticosteroids regulate NMDAR function within the adult brain is relatively sparse, perhaps due to a common belief that NMDAR function is relatively stable in the adult brain. We review recent results from our laboratory and others demonstrating dynamic regulation of NMDAR function by CORT in the adult brain. In addition, we consider the issue of how differences in the early life environment may program differential sensitivity to modulation of NMDAR function by CORT and how this may influence synaptic function during stress. Findings from these studies demonstrate that NMDAR function in the adult hippocampus remains sensitive to even brief exposures to CORT and that the capacity for modulation of NMDAR may be programmed, in part, by the early life environment. Modulation of NMDAR function may contribute to dynamic regulation of synaptic plasticity and adaptation in the face of stress, however enhanced NMDAR function may be implicated in mechanisms of stress related psychopathologies including depression.

  5. Lorentz-Violating Regulator Gauge Fields as the Origin of Dynamical Flavour Oscillations

    CERN Document Server

    Alexandre, Jean; Mavromatos, Nick E

    2013-01-01

    We show how a mass mixing matrix can be generated dynamically, for two massless fermion flavours coupled to a Lorentz invariance violating (LIV) gauge field. The LIV features play the role of a regulator for the gap equations, and the non-analytic dependence of the dynamical masses, as functions of the gauge coupling, allows to consider the limit where the LIV gauge field eventually decouples from the fermions. Lorentz invariance is then recovered, to describe the oscillation between two free fermion flavours, and we check that the finite dynamical masses are the only effects of the original LIV theory. We also discuss briefly a connection of our results with the case of Majorana neutrinos in both, the standard model, where only left-handed (active) neutrinos are considered, and extensions thereof, with sterile right-handed neutrinos.

  6. Evidence for dynamic network regulation of Drosophila photoreceptor function from mutants lacking the neurotransmitter histamine

    Directory of Open Access Journals (Sweden)

    An eDau

    2016-03-01

    Full Text Available Synaptic feedback from interneurons to photoreceptors can help to optimize visual information flow by balancing its allocation on retinal pathways under changing light conditions. But little is known about how this critical network operation is regulated dynamically. Here, we investigate this question by comparing signaling properties and performance of wild-type Drosophila R1-R6 photoreceptors to those of the hdcJK910 mutant, which lacks the neurotransmitter histamine and therefore cannot transmit information to interneurons. Recordings show that hdcJK910 photoreceptors sample similar amounts of information from naturalistic stimulation to wild-type photoreceptors, but this information is packaged in smaller responses, especially under bright illumination. Analyses reveal how these altered dynamics primarily resulted from network overload that affected hdcJK910 photoreceptors in two ways. First, the missing inhibitory histamine input to interneurons almost certainly depolarized them irrevocably, which in turn increased their excitatory feedback to hdcJK910 R1-R6s. This tonic excitation depolarized the photoreceptors to artificially high potentials, reducing their operational range. Second, rescuing histamine input to interneurons in hdcJK910 mutant also restored their normal phasic feedback modulation to R1-R6s, causing photoreceptor output to accentuate dynamic intensity differences at bright illumination, similar to the wild-type. These results provide mechanistic explanations of how synaptic feedback connections optimize information packaging in photoreceptor output and novel insight into the operation and design of dynamic network regulation of sensory neurons.

  7. Noncoding transcription by alternative rna polymerases dynamically regulates an auxin-driven chromatin loop

    KAUST Repository

    Ariel, Federico D.

    2014-08-01

    The eukaryotic epigenome is shaped by the genome topology in three-dimensional space. Dynamic reversible variations in this epigenome structure directly influence the transcriptional responses to developmental cues. Here, we show that the Arabidopsis long intergenic noncoding RNA (lincRNA) APOLO is transcribed by RNA polymerases II and V in response to auxin, a phytohormone controlling numerous facets of plant development. This dual APOLO transcription regulates the formation of a chromatin loop encompassing the promoter of its neighboring gene PID, a key regulator of polar auxin transport. Altering APOLO expression affects chromatin loop formation, whereas RNA-dependent DNA methylation, active DNA demethylation, and Polycomb complexes control loop dynamics. This dynamic chromatin topology determines PID expression patterns. Hence, the dual transcription of a lincRNA influences local chromatin topology and directs dynamic auxin-controlled developmental outputs on neighboring genes. This mechanism likely underscores the adaptive success of plants in diverse environments and may be widespread in eukaryotes. © 2014 Elsevier Inc.

  8. A voltage regulator system with dynamic bandwidth boosting for passive UHF RFID transponders

    International Nuclear Information System (INIS)

    Shen Jinpeng; Wang Xin'an; Liu Shan; Li Shoucheng; Ruan Zhengkun

    2013-01-01

    This paper presents a voltage regulator system for passive UHF RFID transponders, which contains a rectifier, a limiter, and a regulator. The rectifier achieves power by rectifying the incoming RF energy. Due to the huge variation of the rectified voltage, a limiter at the rectifier output is used to clamp the rectified voltage. In this paper, the design of a limiter circuit is discussed in detail, which can provide a stable limiting voltage with low sensitivity to temperature variation and process dispersion. The key aspect of the voltage regulator system is the dynamic bandwidth boosting in the regulator. By sensing the excess current that is bypassed in the limiter during periods of excess energy, the bias current as well as the bandwidth of the regulator are increased, the output supply voltage can recover quickly from line transients during the periods of no RF energy to a full blast of RF energy. This voltage regulator system is implemented in a 0.18 μm CMOS process. (semiconductor integrated circuits)

  9. Application of non-linear discretetime feedback regulators with assignable closed-loop dynamics

    Directory of Open Access Journals (Sweden)

    Dubljević Stevan

    2003-01-01

    Full Text Available In the present work the application of a new approach is demonstrated to a discrete-time state feedback regulator synthesis with feedback linearization and pole-placement for non-linear discrete-time systems. Under the simultaneous implementation of a non-linear coordinate transformation and a non-linear state feedback law computed through the solution of a system of non-linear functional equations, both the feedback linearization and pole-placement design objectives were accomplished. The non-linear state feedback regulator synthesis method was applied to a continuous stirred tank reactor (CSTR under non-isothermal operating conditions that exhibits steady-state multiplicity. The control objective was to regulate the reactor at the middle unstable steady state by manipulating the rate of input heat in the reactor. Simulation studies were performed to evaluate the performance of the proposed non-linear state feedback regulator, as it was shown a non-linear state feedback regulator clearly outperformed a standard linear one, especially in the presence of adverse disturbance under which linear regulation at the unstable steady state was not feasible.

  10. VRK1 regulates Cajal body dynamics and protects coilin from proteasomal degradation in cell cycle.

    Science.gov (United States)

    Cantarero, Lara; Sanz-García, Marta; Vinograd-Byk, Hadar; Renbaum, Paul; Levy-Lahad, Ephrat; Lazo, Pedro A

    2015-06-12

    Cajal bodies (CBs) are nuclear organelles associated with ribonucleoprotein functions and RNA maturation. CBs are assembled on coilin, its main scaffold protein, in a cell cycle dependent manner. The Ser-Thr VRK1 (vaccinia-related kinase 1) kinase, whose activity is also cell cycle regulated, interacts with and phosphorylates coilin regulating assembly of CBs. Coilin phosphorylation is not necessary for its interaction with VRK1, but it occurs in mitosis and regulates coilin stability. Knockdown of VRK1 or VRK1 inactivation by serum deprivation causes a loss of coilin phosphorylation in Ser184 and of CBs formation, which are rescued with an active VRK1, but not by kinase-dead VRK1. The phosphorylation of coilin in Ser184 occurs during mitosis before assembly of CBs. Loss of coilin phosphorylation results in disintegration of CBs, and of coilin degradation that is prevented by proteasome inhibitors. After depletion of VRK1, coilin is ubiquitinated in nuclei, which is partly mediated by mdm2, but its proteasomal degradation occurs in cytosol and is prevented by blocking its nuclear export. We conclude that VRK1 is a novel regulator of CBs dynamics and stability in cell cycle by protecting coilin from ubiquitination and degradation in the proteasome, and propose a model of CB dynamics.

  11. Quantitative analysis of proteome and lipidome dynamics reveals functional regulation of global lipid metabolism

    DEFF Research Database (Denmark)

    Casanovas, Albert; Sprenger, Richard R; Tarasov, Kirill

    2015-01-01

    Elucidating how and to what extent lipid metabolism is remodeled under changing conditions is essential for understanding cellular physiology. Here, we analyzed proteome and lipidome dynamics to investigate how regulation of lipid metabolism at the global scale supports remodeling of cellular...... differential turnover of lipid droplet-associated triacylglycerols and sterol esters during respiratory growth, that sphingolipid metabolism is regulated in a previously unrecognized growth stage-specific manner, and that endogenous synthesis of unsaturated fatty acids constitutes an in vivo upstream activator...... of peroxisomal biogenesis, via the heterodimeric Oaf1/Pip2 transcription factor. Our work demonstrates the pivotal role of lipid metabolism in adaptive processes and provides a resource to investigate its regulation at the cellular level....

  12. How lateral connections and spiking dynamics may separate multiple objects moving together.

    Directory of Open Access Journals (Sweden)

    Benjamin D Evans

    Full Text Available Over successive stages, the ventral visual system of the primate brain develops neurons that respond selectively to particular objects or faces with translation, size and view invariance. The powerful neural representations found in Inferotemporal cortex form a remarkably rapid and robust basis for object recognition which belies the difficulties faced by the system when learning in natural visual environments. A central issue in understanding the process of biological object recognition is how these neurons learn to form separate representations of objects from complex visual scenes composed of multiple objects. We show how a one-layer competitive network comprised of 'spiking' neurons is able to learn separate transformation-invariant representations (exemplified by one-dimensional translations of visual objects that are always seen together moving in lock-step, but separated in space. This is achieved by combining 'Mexican hat' functional lateral connectivity with cell firing-rate adaptation to temporally segment input representations of competing stimuli through anti-phase oscillations (perceptual cycles. These spiking dynamics are quickly and reliably generated, enabling selective modification of the feed-forward connections to neurons in the next layer through Spike-Time-Dependent Plasticity (STDP, resulting in separate translation-invariant representations of each stimulus. Variations in key properties of the model are investigated with respect to the network's ability to develop appropriate input representations and subsequently output representations through STDP. Contrary to earlier rate-coded models of this learning process, this work shows how spiking neural networks may learn about more than one stimulus together without suffering from the 'superposition catastrophe'. We take these results to suggest that spiking dynamics are key to understanding biological visual object recognition.

  13. Express company’s vehicle routing optimization by multiple-dynamic saving algorithm

    Directory of Open Access Journals (Sweden)

    Junchao Liu

    2014-05-01

    Full Text Available Purpose: According to the disorder in circulation commuting and crossover commuting of SF company which is the China’s largest private express delivery service provider, the study uses the Saving Algorithm to make the vehicle routing and resources optimized, on this basis, proposes innovative improvements with Saving Algorithm and then applies it in every distribution center of SF forming a "multi-dynamic" type of Saving Algorithm to ensure both cost savings and timeliness. This method can be generalized for all express company to get the vehicle routing optimized.Design/methodology/approach: As the special transportation requirements of express companies, this study optimizes the vehicle route based on Saving Algorithm, uses multiple-dynamic Saving Algorithm, and considers the timeliness requirements of the express company to achieve a balance of cost and timeliness.Findings: The main finding is that a new method proposed which there can be a balance improvement for both cost and timeliness to optimize the vehicle route of express company. Calculation example validates the effectiveness of the model established and solving method.Practical implications: It is a widespread practice that by setting up model and parameters for the objectives, express company can maintain the balances between cost and timeliness and achieve the optimized vehicle route.Originality/value: It proposes innovative improvements, takes SF express company as an example, with Saving Algorithm which can be applied in every distribution center of express company to ensure the balance improvement for both cost and timeliness, and has a great practical significance to the transportation network and path optimization of express companies.

  14. Dynamic routing control in heterogeneous tactical networks with multiple traffic priorities

    Science.gov (United States)

    Fecko, Mariusz A.; Wong, Larry; Kang, Jaewong; Cichocki, Andrzej; Kaul, Vikram; Samtani, Sunil

    2012-05-01

    To efficiently use alternate paths during periods of congestion, we have devised prioritized Dynamic Routing Control Agent (pDRCA) that (1) selects best links to meet the bandwidth and delay requirements of traffic, (2) provides load-balancing and traffic prioritization when multiple topologies are available, and (3) handles changes in link quality and traffic demand, and link outages. pDRCA provides multiplatform load balancing to maximize SATCOM (both P2P and multi-point) and airborne links utilization. It influences link selection by configuring the cost metrics on a router's interface, which does not require any changes to the routing protocol itself. It supports service differentiation of multiple traffic priorities by providing more network resources to the highest priority flows. pDRCA does so by solving an optimization problem to find optimal links weights that increase throughput and decrease E2E delay; avoid congested, low quality, and long delay links; and exploit path diversity in the network. These optimal link weights are sent to the local agents to be configured on individual routers per traffic priority. The pDRCA optimization algorithm has been proven effective in improving application performance. We created a variety of different test scenarios by varying traffic profile and link behavior (stable links, varying capacity, and link outages). In the scenarios where high priority traffic experienced significant loss without pDRCA, the average loss was reduced from 49.5% to 13% and in some cases dropped to 0%. Currently, pDRCA is integrated with an open-source software router and priority queues on Linux as a component of Open Tactical Router (OTR), which is being developed by ONR DTCN program.

  15. Quantum critical matter. Quantum phase transitions with multiple dynamics and Weyl superconductors

    International Nuclear Information System (INIS)

    Meng, Tobias

    2012-01-01

    In this PhD thesis, the physics of quantum critical matter and exotic quantum state close to quantum phase transitions is investigated. We will focus on three different examples that highlight some of the interesting phenomena related to quantum phase transitions. Firstly, we discuss the physics of quantum phase transitions in quantum wires as a function of an external gate voltage when new subbands are activated. We find that at these transitions, strong correlations lead to the formation of an impenetrable gas of polarons, and identify criteria for possible instabilities in the spin- and charge sectors of the model. Our analysis is based on the combination of exact resummations, renormalization group techniques and Luttinger liquid approaches. Secondly, we turn to the physics of multiple divergent time scales close to a quantum critical point. Using an appropriately generalized renormalization group approach, we identify that the presence of multiple dynamics at a quantum phase transition can lead to the emergence of new critical scaling exponents and thus to the breakdown of the usual scaling schemes. We calculate the critical behavior of various thermodynamic properties and detail how unusual physics can arise. It is hoped that these results might be helpful for the interpretation of experimental scaling puzzles close to quantum critical points. Thirdly, we turn to the physics of topological transitions, and more precisely the physics of Weyl superconductors. The latter are the superconducting variant of the topologically non-trivial Weyl semimetals, and emerge at the quantum phase transition between a topological superconductor and a normal insulator upon perturbing the transition with a time reversal symmetry breaking perturbation, such as magnetism. We characterize the topological properties of Weyl superconductors and establish a topological phase diagram for a particular realization in heterostructures. We discuss the physics of vortices in Weyl

  16. Multiple steps in the regulation of transcription-factor level and activity

    NARCIS (Netherlands)

    Calkhoven, CF; Ab, G

    1996-01-01

    This review focuses on the regulation of transcription factors, many of which are DNA-binding proteins that recognize cis-regulatory elements of target genes and are the most direct regulators of gene transcription. Transcription factors serve as integration centres of the different

  17. 76 FR 14548 - Federal Acquisition Regulation; Requirements for Acquisitions Pursuant to Multiple-Award Contracts

    Science.gov (United States)

    2011-03-16

    ... FSS contracts on or after May 16, 2011. (4) The ordering procedures for BPAs in FAR 8.405-3(c) are... of the following methods: Regulations.gov : http://www.regulations.gov . Submit comments via the... changes to strengthen the use of competition in task- and delivery-order contracts, the Defense...

  18. Inhibition of host extracellular signal-regulated kinase (ERK) activation decreases new world alphavirus multiplication in infected cells

    International Nuclear Information System (INIS)

    Voss, Kelsey; Amaya, Moushimi; Mueller, Claudius; Roberts, Brian; Kehn-Hall, Kylene; Bailey, Charles; Petricoin, Emanuel; Narayanan, Aarthi

    2014-01-01

    New World alphaviruses belonging to the family Togaviridae are classified as emerging infectious agents and Category B select agents. Our study is focused on the role of the host extracellular signal-regulated kinase (ERK) in the infectious process of New World alphaviruses. Infection of human cells by Venezuelan equine encephalitis virus (VEEV) results in the activation of the ERK-signaling cascade. Inhibition of ERK1/2 by the small molecule inhibitor Ag-126 results in inhibition of viral multiplication. Ag-126-mediated inhibition of VEEV was due to potential effects on early and late stages of the infectious process. While expression of viral proteins was down-regulated in Ag-126 treated cells, we did not observe any influence of Ag-126 on the nuclear distribution of capsid. Finally, Ag-126 exerted a broad-spectrum inhibitory effect on New World alphavirus multiplication, thus indicating that the host kinase, ERK, is a broad-spectrum candidate for development of novel therapeutics against New World alphaviruses. - Highlights: • VEEV infection activated multiple components of the ERK signaling cascade. • Inhibition of ERK activation using Ag-126 inhibited VEEV multiplication. • Activation of ERK by Ceramide C6 increased infectious titers of TC-83. • Ag-126 inhibited virulent strains of all New World alphaviruses. • Ag-126 treatment increased percent survival of infected cells

  19. Inhibition of host extracellular signal-regulated kinase (ERK) activation decreases new world alphavirus multiplication in infected cells

    Energy Technology Data Exchange (ETDEWEB)

    Voss, Kelsey; Amaya, Moushimi [National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, 10650 Pyramid Place, Manassas, VA (United States); Mueller, Claudius [Center for Applied Proteomics and Personalized Medicine, George Mason University, 10900 University Boulevard, Manassas, VA (United States); Roberts, Brian [Leidos Health Life Sciences, 5202 Presidents Court, Suite 110, Frederick, MD (United States); Kehn-Hall, Kylene; Bailey, Charles [National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, 10650 Pyramid Place, Manassas, VA (United States); Petricoin, Emanuel [Center for Applied Proteomics and Personalized Medicine, George Mason University, 10900 University Boulevard, Manassas, VA (United States); Narayanan, Aarthi, E-mail: anaraya1@gmu.edu [National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, 10650 Pyramid Place, Manassas, VA (United States)

    2014-11-15

    New World alphaviruses belonging to the family Togaviridae are classified as emerging infectious agents and Category B select agents. Our study is focused on the role of the host extracellular signal-regulated kinase (ERK) in the infectious process of New World alphaviruses. Infection of human cells by Venezuelan equine encephalitis virus (VEEV) results in the activation of the ERK-signaling cascade. Inhibition of ERK1/2 by the small molecule inhibitor Ag-126 results in inhibition of viral multiplication. Ag-126-mediated inhibition of VEEV was due to potential effects on early and late stages of the infectious process. While expression of viral proteins was down-regulated in Ag-126 treated cells, we did not observe any influence of Ag-126 on the nuclear distribution of capsid. Finally, Ag-126 exerted a broad-spectrum inhibitory effect on New World alphavirus multiplication, thus indicating that the host kinase, ERK, is a broad-spectrum candidate for development of novel therapeutics against New World alphaviruses. - Highlights: • VEEV infection activated multiple components of the ERK signaling cascade. • Inhibition of ERK activation using Ag-126 inhibited VEEV multiplication. • Activation of ERK by Ceramide C6 increased infectious titers of TC-83. • Ag-126 inhibited virulent strains of all New World alphaviruses. • Ag-126 treatment increased percent survival of infected cells.

  20. Ultrafast conductivity dynamics in optically excited InGaN/GaN multiple quantum wells, observed by transient THz spectroscopy

    DEFF Research Database (Denmark)

    Turchinovich, Dmitry; Porte, Henrik; Cooke, David

    2010-01-01

    We investigate ultrafast carrier dynamics in photoexcited InGaN/GaN multiple quantum wells by time-resolved terahertz spectroscopy. The initially very strong built-in piezoelectric field is screened upon photoexcitation by the polarized carriers, and is gradually restored as the carriers recombin...

  1. ATX-2, the C. elegans Ortholog of Human Ataxin-2, Regulates Centrosome Size and Microtubule Dynamics.

    Science.gov (United States)

    Stubenvoll, Michael D; Medley, Jeffrey C; Irwin, Miranda; Song, Mi Hye

    2016-09-01

    Centrosomes are critical sites for orchestrating microtubule dynamics, and exhibit dynamic changes in size during the cell cycle. As cells progress to mitosis, centrosomes recruit more microtubules (MT) to form mitotic bipolar spindles that ensure proper chromosome segregation. We report a new role for ATX-2, a C. elegans ortholog of Human Ataxin-2, in regulating centrosome size and MT dynamics. ATX-2, an RNA-binding protein, forms a complex with SZY-20 in an RNA-independent fashion. Depleting ATX-2 results in embryonic lethality and cytokinesis failure, and restores centrosome duplication to zyg-1 mutants. In this pathway, SZY-20 promotes ATX-2 abundance, which inversely correlates with centrosome size. Centrosomes depleted of ATX-2 exhibit elevated levels of centrosome factors (ZYG-1, SPD-5, γ-Tubulin), increasing MT nucleating activity but impeding MT growth. We show that ATX-2 influences MT behavior through γ-Tubulin at the centrosome. Our data suggest that RNA-binding proteins play an active role in controlling MT dynamics and provide insight into the control of proper centrosome size and MT dynamics.

  2. ATX-2, the C. elegans Ortholog of Human Ataxin-2, Regulates Centrosome Size and Microtubule Dynamics.

    Directory of Open Access Journals (Sweden)

    Michael D Stubenvoll

    2016-09-01

    Full Text Available Centrosomes are critical sites for orchestrating microtubule dynamics, and exhibit dynamic changes in size during the cell cycle. As cells progress to mitosis, centrosomes recruit more microtubules (MT to form mitotic bipolar spindles that ensure proper chromosome segregation. We report a new role for ATX-2, a C. elegans ortholog of Human Ataxin-2, in regulating centrosome size and MT dynamics. ATX-2, an RNA-binding protein, forms a complex with SZY-20 in an RNA-independent fashion. Depleting ATX-2 results in embryonic lethality and cytokinesis failure, and restores centrosome duplication to zyg-1 mutants. In this pathway, SZY-20 promotes ATX-2 abundance, which inversely correlates with centrosome size. Centrosomes depleted of ATX-2 exhibit elevated levels of centrosome factors (ZYG-1, SPD-5, γ-Tubulin, increasing MT nucleating activity but impeding MT growth. We show that ATX-2 influences MT behavior through γ-Tubulin at the centrosome. Our data suggest that RNA-binding proteins play an active role in controlling MT dynamics and provide insight into the control of proper centrosome size and MT dynamics.

  3. Fast Multispectral Optoacoustic Tomography (MSOT) for Dynamic Imaging of Pharmacokinetics and Biodistribution in Multiple Organs

    Science.gov (United States)

    Taruttis, Adrian; Morscher, Stefan; Burton, Neal C.; Razansky, Daniel; Ntziachristos, Vasilis

    2012-01-01

    The characterization of pharmacokinetic and biodistribution profiles is an essential step in the development process of new candidate drugs or imaging agents. Simultaneously, the assessment of organ function related to the uptake and clearance of drugs is of great importance. To this end, we demonstrate an imaging platform capable of high-rate characterization of the dynamics of fluorescent agents in multiple organs using multispectral optoacoustic tomography (MSOT). A spatial resolution of approximately 150 µm through mouse cross-sections allowed us to image blood vessels, the kidneys, the liver and the gall bladder. In particular, MSOT was employed to characterize the removal of indocyanine green from the systemic circulation and its time-resolved uptake in the liver and gallbladder. Furthermore, it was possible to track the uptake of a carboxylate dye in separate regions of the kidneys. The results demonstrate the acquisition of agent concentration metrics at rates of 10 samples per second at a single wavelength and 17 s per multispectral sample with 10 signal averages at each of 5 wavelengths. Overall, such imaging performance introduces previously undocumented capabilities of fast, high resolution in vivo imaging of the fate of optical agents for drug discovery and basic biological research. PMID:22295087

  4. Dynamic load mitigation using dissipative elastic metamaterials with multiple Maxwell-type oscillators

    Science.gov (United States)

    Alamri, Sagr; Li, Bing; Tan, K. T.

    2018-03-01

    Dissipative elastic metamaterials have attracted increased attention in recent times. This paper presents the development of a dissipative elastic metamaterial with multiple Maxwell-type resonators for stress wave attenuation. The mechanism of the dissipation effect on the vibration characteristics is systematically investigated by mass-spring-damper models with single and dual resonators. Based on the parameter optimization, it is revealed that a broadband wave attenuation region (stopping band) can be obtained by properly utilizing interactions from resonant motions and viscoelastic effects of the Maxwell-type oscillators. The relevant numerical verifications are conducted for various cases, and excellent agreement between the numerical and theoretical frequency response functions is shown. The design of this dissipative metamaterial system is further applied for dynamic load mitigation and blast wave attenuation. Moreover, the transient response in the continuum model is designed and analyzed for more robust design. By virtue of the bandgap merging effect induced by the Maxwell-type damper, the transient blast wave can be almost completely suppressed in the low frequency range. A significantly improved performance of the proposed dissipative metamaterials for stress wave mitigation is verified in both time and frequency domains.

  5. Modern drug design: the implication of using artificial neuronal networks and multiple molecular dynamic simulations

    Science.gov (United States)

    Yakovenko, Oleksandr; Jones, Steven J. M.

    2018-01-01

    We report the implementation of molecular modeling approaches developed as a part of the 2016 Grand Challenge 2, the blinded competition of computer aided drug design technologies held by the D3R Drug Design Data Resource (https://drugdesigndata.org/). The challenge was focused on the ligands of the farnesoid X receptor (FXR), a highly flexible nuclear receptor of the cholesterol derivative chenodeoxycholic acid. FXR is considered an important therapeutic target for metabolic, inflammatory, bowel and obesity related diseases (Expert Opin Drug Metab Toxicol 4:523-532, 2015), but in the context of this competition it is also interesting due to the significant ligand-induced conformational changes displayed by the protein. To deal with these conformational changes we employed multiple simulations of molecular dynamics (MD). Our MD-based protocols were top-ranked in estimating the free energy of binding of the ligands and FXR protein. Our approach was ranked second in the prediction of the binding poses where we also combined MD with molecular docking and artificial neural networks. Our approach showed mediocre results for high-throughput scoring of interactions.

  6. FODA: a novel efficient multiple access protocol for highly dynamic self-organizing networks

    Science.gov (United States)

    Li, Hantao; Liu, Kai; Zhang, Jun

    2005-11-01

    Based on the concept of contention reservation for polling transmission and collision prevention strategy for collision resolution, a fair on-demand access (FODA) protocol for supporting node mobility and multihop architecture in highly dynamic self-organizing networks is proposed. In the protocol, a distributed clustering network architecture formed by self-organizing algorithm and a main idea of reserving channel resources to get polling service are adopted, so that the hidden terminal (HT) and exposed terminal (ET) problems existed in traffic transmission due to multihop architecture and wireless transmission can be eliminated completely. In addition, an improved collision prevention scheme based on binary countdown algorithm (BCA), called fair collision prevention (FCP) algorithm, is proposed to greatly eliminate unfair phenomena existed in contention access of newly active ordinary nodes and completely resolve access collisions. Finally, the performance comparison of the FODA protocol with carrier sense multiple access with collision avoidance (CSMA/CA) and polling protocols by OPNET simulation are presented. Simulation results show that the FODA protocol can overcome the disadvantages of CSMA/CA and polling protocols, and achieve higher throughput, lower average message delay and less average message dropping rate.

  7. The Dynamics of Multiple Pair-Wise Collisions in a Chain for Designing Optimal Shock Amplifiers

    Directory of Open Access Journals (Sweden)

    Bryan Rodgers

    2009-01-01

    Full Text Available The major focus of this work is to examine the dynamics of velocity amplification through pair-wise collisions between multiple masses in a chain, in order to develop useful machines. For instance low-cost machines based on this principle could be used for detailed, very-high acceleration shock-testing of MEMS devices. A theoretical basis for determining the number and mass of intermediate stages in such a velocity amplifier, based on simple rigid body mechanics, is proposed. The influence of mass ratios and the coefficient of restitution on the optimisation of the system is identified and investigated. In particular, two cases are examined: in the first, the velocity of the final mass in the chain (that would have the object under test mounted on it is maximised by defining the ratio of adjacent masses according to a power law relationship; in the second, the energy transfer efficiency of the system is maximised by choosing the mass ratios such that all masses except the final mass come to rest following impact. Comparisons are drawn between both cases and the results are used in proposing design guidelines for optimal shock amplifiers. It is shown that for most practical systems, a shock amplifier with mass ratios based on a power law relationship is optimal and can easily yield velocity amplifications of a factor 5–8 times. A prototype shock testing machine that was made using above principles is briefly introduced.

  8. Efficient traffic grooming with dynamic ONU grouping for multiple-OLT-based access network

    Science.gov (United States)

    Zhang, Shizong; Gu, Rentao; Ji, Yuefeng; Wang, Hongxiang

    2015-12-01

    Fast bandwidth growth urges large-scale high-density access scenarios, where the multiple Passive Optical Networking (PON) system clustered deployment can be adopted as an appropriate solution to fulfill the huge bandwidth demands, especially for a future 5G mobile network. However, the lack of interaction between different optical line terminals (OLTs) results in part of the bandwidth resources waste. To increase the bandwidth efficiency, as well as reduce bandwidth pressure at the edge of a network, we propose a centralized flexible PON architecture based on Time- and Wavelength-Division Multiplexing PON (TWDM PON). It can provide flexible affiliation for optical network units (ONUs) and different OLTs to support access network traffic localization. Specifically, a dynamic ONU grouping algorithm (DGA) is provided to obtain the minimal OLT outbound traffic. Simulation results show that DGA obtains an average 25.23% traffic gain increment under different OLT numbers within a small ONU number situation, and the traffic gain will increase dramatically with the increment of the ONU number. As the DGA can be deployed easily as an application running above the centralized control plane, the proposed architecture can be helpful to improve the network efficiency for future traffic-intensive access scenarios.

  9. Dynamic analysis of piping with multiple damping mechanisms; Analisis dinamico de tuberias con multiples mecanismos de amortiguamiento

    Energy Technology Data Exchange (ETDEWEB)

    Ruiz Lopez, Pablo [Instituto de Investigaciones Electricas, Cuernavaca (Mexico)

    1989-12-31

    This paper describes a damping criterion that allows realizing in a more convenient form the dynamic analysis of piping and structures in general, subjected to independent stimulations, fabricated in different materials and/or damping devices. This criterion, named composed damping, is applicable to the method of modal superimposition. [Espanol] En este trabajo se describe un criterio de amortiguamiento que permite realizar en una forma mas conveniente el analisis dinamico de tuberias y estructuras en general, sujetas a excitaciones independientes, compuestas de diferentes materiales y/o mecanismos de amortiguamiento. Este criterio, denominado amortiguamiento compuesto, es aplicable en el metodo de superposicion modal.

  10. 77 FR 12927 - Federal Acquisition Regulation: Requirements for Acquisitions Pursuant to Multiple-Award Contracts

    Science.gov (United States)

    2012-03-02

    ... original price list in anticipation of multiple layers of price negotiation during the competitive... and safety effects, distributive impacts, and equity). E.O. 13563 emphasizes the importance of...

  11. The Complex Relationship between Liver Cancer and the Cell Cycle: A Story of Multiple Regulations

    Energy Technology Data Exchange (ETDEWEB)

    Bisteau, Xavier [Institute of Molecular and Cell Biology (IMCB), A*STAR (Agency for Science, Technology and Research), 61 Biopolis Drive, Proteos#3-09, Singapore 138673 (Singapore); Caldez, Matias J.; Kaldis, Philipp, E-mail: kaldis@imcb.a-star.edu.sg [Institute of Molecular and Cell Biology (IMCB), A*STAR (Agency for Science, Technology and Research), 61 Biopolis Drive, Proteos#3-09, Singapore 138673 (Singapore); National University of Singapore (NUS), Department of Biochemistry, Singapore 117597 (Singapore)

    2014-01-13

    The liver acts as a hub for metabolic reactions to keep a homeostatic balance during development and growth. The process of liver cancer development, although poorly understood, is related to different etiologic factors like toxins, alcohol, or viral infection. At the molecular level, liver cancer is characterized by a disruption of cell cycle regulation through many molecular mechanisms. In this review, we focus on the mechanisms underlying the lack of regulation of the cell cycle during liver cancer, focusing mainly on hepatocellular carcinoma (HCC). We also provide a brief summary of novel therapies connected to cell cycle regulation.

  12. Cell autonomous and microenvironmental regulation of tumor progression in precursor states of multiple myeloma.

    Science.gov (United States)

    Manier, Salomon; Kawano, Yawara; Bianchi, Giada; Roccaro, Aldo M; Ghobrial, Irene M

    2016-07-01

    Multiple myeloma is a plasma cell malignancy evolving in the bone marrow and leading to end organ damage such as bone lesions, cytopenias, and kidney failure. This review delineates recent advances in the molecular mechanisms leading to tumor progression in multiple myeloma. Two different aspects enable tumor expansion: cell autonomous through genomic alterations in the tumor clone and noncell autonomous deregulations in the bone marrow tumor microenvironment. These alterations provide the framework for the continuous progression of multiple myeloma from early precursor conditions such as monoclonal gammopathy of undetermined significance and smoldering multiple myeloma to overt multiple myeloma. In this review, we discuss recent findings in the genomic alterations that occur in the tumor clone such as somatic genomic mutations, copy number variation and chromosomal translocation, and delineate noncell autonomous deregulations in which tumor cells take advantage of a permissive microenvironment to further proliferate. The latter compartment includes interaction with bone marrow stromal cells, osteoblasts, osteoclasts, and immune escape. Understanding the mechanisms that lead tumor progression from early stages to overt multiple myeloma could guide to more effective therapies and therefore prevent disease progression.

  13. Bayesian inference based modelling for gene transcriptional dynamics by integrating multiple source of knowledge

    Directory of Open Access Journals (Sweden)

    Wang Shu-Qiang

    2012-07-01

    Full Text Available Abstract Background A key challenge in the post genome era is to identify genome-wide transcriptional regulatory networks, which specify the interactions between transcription factors and their target genes. Numerous methods have been developed for reconstructing gene regulatory networks from expression data. However, most of them are based on coarse grained qualitative models, and cannot provide a quantitative view of regulatory systems. Results A binding affinity based regulatory model is proposed to quantify the transcriptional regulatory network. Multiple quantities, including binding affinity and the activity level of transcription factor (TF are incorporated into a general learning model. The sequence features of the promoter and the possible occupancy of nucleosomes are exploited to estimate the binding probability of regulators. Comparing with the previous models that only employ microarray data, the proposed model can bridge the gap between the relative background frequency of the observed nucleotide and the gene's transcription rate. Conclusions We testify the proposed approach on two real-world microarray datasets. Experimental results show that the proposed model can effectively identify the parameters and the activity level of TF. Moreover, the kinetic parameters introduced in the proposed model can reveal more biological sense than previous models can do.

  14. mir-30d Regulates multiple genes in the autophagy pathway and impairs autophagy process in human cancer cells

    International Nuclear Information System (INIS)

    Yang, Xiaojun; Zhong, Xiaomin; Tanyi, Janos L.; Shen, Jianfeng; Xu, Congjian; Gao, Peng; Zheng, Tim M.; DeMichele, Angela; Zhang, Lin

    2013-01-01

    Highlights: ► Gene set enrichment analysis indicated mir-30d might regulate the autophagy pathway. ► mir-30d represses the expression of BECN1, BNIP3L, ATG12, ATG5 and ATG2. ► BECN1, BNIP3L, ATG12, ATG5 and ATG2 are direct targets of mir-30d. ► mir-30d inhibits autophagosome formation and LC3B-I conversion to LC3B-II. ► mir-30d regulates the autophagy process. -- Abstract: In human epithelial cancers, the microRNA (miRNA) mir-30d is amplified with high frequency and serves as a critical oncomir by regulating metastasis, apoptosis, proliferation, and differentiation. Autophagy, a degradation pathway for long-lived protein and organelles, regulates the survival and death of many cell types. Increasing evidence suggests that autophagy plays an important function in epithelial tumor initiation and progression. Using a combined bioinformatics approach, gene set enrichment analysis, and miRNA target prediction, we found that mir-30d might regulate multiple genes in the autophagy pathway including BECN1, BNIP3L, ATG12, ATG5, and ATG2. Our further functional experiments demonstrated that the expression of these core proteins in the autophagy pathway was directly suppressed by mir-30d in cancer cells. Finally, we showed that mir-30d regulated the autophagy process by inhibiting autophagosome formation and LC3B-I conversion to LC3B-II. Taken together, our results provide evidence that the oncomir mir-30d impairs the autophagy process by targeting multiple genes in the autophagy pathway. This result will contribute to understanding the molecular mechanism of mir-30d in tumorigenesis and developing novel cancer therapy strategy

  15. MULTIPLE STABLE PERIODIC SOLUTIONS IN A MODEL FOR THE HORMONAL REGULATION OF THE MENSTRUAL CYCLE

    Science.gov (United States)

    ABSTRACTThe pituitary hormones, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and the ovarian hormones, estradiol (E2), progesterone (P4), and inhibin (Ih), are five hormones important for the regulation and maintenance of the human menstrual cycle. The...

  16. Rgs1 regulates multiple Gα subunits in Magnaporthe pathogenesis, asexual growth and thigmotropism

    OpenAIRE

    Liu, Hao; Suresh, Angayarkanni; Willard, Francis S; Siderovski, David P; Lu, Shen; Naqvi, Naweed I

    2007-01-01

    Regulators of G-protein signaling (RGS proteins) negatively regulate heterotrimeric G-protein cascades that enable eukaryotic cells to perceive and respond to external stimuli. The rice-blast fungus Magnaporthe grisea forms specialized infection structures called appressoria in response to inductive surface cues. We isolated Magnaporthe RGS1 in a screen for mutants that form precocious appressoria on non-inductive surfaces. We report that a thigmotropic cue is necessary for initiating appress...

  17. Dynamic stereotype and vegetative regulation corection in childrens with effects of organic lesion of nervous system

    Directory of Open Access Journals (Sweden)

    Наталія Юріївна Гришуніна

    2015-08-01

    Full Text Available Aim of research. An assessment of the CNS state, neuropsychological indicators and influence of the modern methods of physical rehabilitation on the dynamics of vegetative adaptive and compensatory brain systems in patients with effects of an early organic lesion of nervous system.Materials and methods of research. There were examined and treated 20 children 7-11 years old. An assessment of vegetative homeostasis was carried out using cardiointervalography (CIG, neuropsychic functions and deficiency of statomotor development – the method of Luriya neuropsychological testing. The children of the first group (10 persons underwent massage and therapeutic physical training with special attention to the dynamic stereotype in complex with generally developmental, breathing, special passive and active, static and dynamic exercises, postisometric relaxation, massotherapy. The patients of the second group (10 persons underwent traditional therapeutic physical training and massage.Results of research. It was observed an inhibition of the humoral control of heart rate in examined children and at the same time an activation of sympathetic system. As a result it was detected an increase of the stress index of compensatory reactions of organism (stress index SI — 124 un. at the norm 65,0 ud.. Neuropsychological features of these patients indicated the presence of the left hemispheric and less right hemispheric deficiency, dysfunction of subcortical and stem structures.The use of the complex methodology of rehabilitation with special attention to the dynamic stereotype and manual therapy according to the aspects of genesis of myofascial dysfunction favored an optimization of the stress of compensatory mechanisms of organism (SI — 51,0 un.. In the second group it was observed a stable activity of sympathetic regulation of the heart rate compared with indicators before treatment and an insignificant decrease of the stress index of vegetative balance (SI

  18. Algorithm of dynamic regulation of a system of duct, for a high accuracy climatic system

    Science.gov (United States)

    Arbatskiy, A. A.; Afonina, G. N.; Glazov, V. S.

    2017-11-01

    Currently, major part of climatic system, are stationary in projected mode only. At the same time, many modern industrial sites, require constant or periodical changes in technological process. That is 80% of the time, the industrial site is not require ventilation system in projected mode and high precision of climatic parameters must maintain. While that not constantly is in use for climatic systems, which use in parallel for different rooms, we will be have a problem for balance of duct system. For this problem, was created the algorithm for quantity regulation, with minimal changes. Dynamic duct system: Developed of parallel control system of air balance, with high precision of climatic parameters. The Algorithm provide a permanent pressure in main duct, in different a flow of air. Therefore, the ending devises air flow have only one parameter for regulation - flaps open area. Precision of regulation increase and the climatic system provide high precision for temperature and humidity (0,5C for temperature, 5% for relative humidity). Result: The research has been made in CFD-system - PHOENICS. Results for velocity of air in duct, for pressure of air in duct for different operation mode, has been obtained. Equation for air valves positions, with different parameters for climate in room’s, has been obtained. Energy saving potential for dynamic duct system, for different types of a rooms, has been calculated.

  19. Carotenoid Biosynthetic Pathways Are Regulated by a Network of Multiple Cascades of Alternative Sigma Factors in Azospirillum brasilense Sp7.

    Science.gov (United States)

    Rai, Ashutosh Kumar; Dubey, Ashutosh Prakash; Kumar, Santosh; Dutta, Debashis; Mishra, Mukti Nath; Singh, Bhupendra Narain; Tripathi, Anil Kumar

    2016-11-01

    Carotenoids constitute an important component of the defense system against photooxidative stress in bacteria. In Azospirillum brasilense Sp7, a nonphotosynthetic rhizobacterium, carotenoid synthesis is controlled by a pair of extracytoplasmic function sigma factors (RpoEs) and their cognate zinc-binding anti-sigma factors (ChrRs). Its genome harbors two copies of the gene encoding geranylgeranyl pyrophosphate synthase (CrtE), the first critical step in the carotenoid biosynthetic pathway in bacteria. Inactivation of each of two crtE paralogs found in A. brasilense caused reduction in carotenoid content, suggesting their involvement in carotenoid synthesis. However, the effect of crtE1 deletion was more pronounced than that of crtE2 deletion. Out of the five paralogs of rpoH in A. brasilense, overexpression of rpoH1 and rpoH2 enhanced carotenoid synthesis. Promoters of crtE2 and rpoH2 were found to be dependent on RpoH2 and RpoE1, respectively. Using a two-plasmid system in Escherichia coli, we have shown that the crtE2 gene of A. brasilense Sp7 is regulated by two cascades of sigma factors: one consisting of RpoE1and RpoH2 and the other consisting of RpoE2 and RpoH1. In addition, expression of crtE1 was upregulated indirectly by RpoE1 and RpoE2. This study shows, for the first time in any carotenoid-producing bacterium, that the regulation of carotenoid biosynthetic pathway involves a network of multiple cascades of alternative sigma factors. Carotenoids play a very important role in coping with photooxidative stress in prokaryotes and eukaryotes. Although extracytoplasmic function (ECF) sigma factors are known to directly regulate the expression of carotenoid biosynthetic genes in bacteria, regulation of carotenoid biosynthesis by one or multiple cascades of sigma factors had not been reported. This study provides the first evidence of the involvement of multiple cascades of sigma factors in the regulation of carotenoid synthesis in any bacterium by showing the

  20. Multiple processes regulate long-term population dynamics of sea urchins on Mediterranean rocky reefs.

    Directory of Open Access Journals (Sweden)

    Bernat Hereu

    Full Text Available We annually monitored the abundance and size structure of herbivorous sea urchin populations (Paracentrotus lividus and Arbacia lixula inside and outside a marine reserve in the Northwestern Mediterranean on two distinct habitats (boulders and vertical walls over a period of 20 years, with the aim of analyzing changes at different temporal scales in relation to biotic and abiotic drivers. P. lividus exhibited significant variability in density over time on boulder bottoms but not on vertical walls, and temporal trends were not significantly different between the protection levels. Differences in densities were caused primarily by variance in recruitment, which was less pronounced inside the MPA and was correlated with adult density, indicating density-dependent recruitment under high predation pressure, as well as some positive feedback mechanisms that may facilitate higher urchin abundances despite higher predator abundance. Populations within the reserve were less variable in abundance and did not exhibit the hyper-abundances observed outside the reserve, suggesting that predation effects maybe more subtle than simply lowering the numbers of urchins in reserves. A. lixula densities were an order of magnitude lower than P. lividus densities and varied within sites and over time on boulder bottoms but did not differ between protection levels. In December 2008, an exceptionally violent storm reduced sea urchin densities drastically (by 50% to 80% on boulder substrates, resulting in the lowest values observed over the entire study period, which remained at that level for at least two years (up to the present. Our results also showed great variability in the biological and physical processes acting at different temporal scales. This study highlights the need for appropriate temporal scales for studies to fully understand ecosystem functioning, the concepts of which are fundamental to successful conservation and management.

  1. Rgs1 regulates multiple Gα subunits in Magnaporthe pathogenesis, asexual growth and thigmotropism

    Science.gov (United States)

    Liu, Hao; Suresh, Angayarkanni; Willard, Francis S; Siderovski, David P; Lu, Shen; Naqvi, Naweed I

    2007-01-01

    Regulators of G-protein signaling (RGS proteins) negatively regulate heterotrimeric G-protein cascades that enable eukaryotic cells to perceive and respond to external stimuli. The rice-blast fungus Magnaporthe grisea forms specialized infection structures called appressoria in response to inductive surface cues. We isolated Magnaporthe RGS1 in a screen for mutants that form precocious appressoria on non-inductive surfaces. We report that a thigmotropic cue is necessary for initiating appressoria and for accumulating cAMP. Similar to an RGS1-deletion strain, magAG187S (RGS-insensitive Gαs) and magAQ208L (GTPase-dead) mutants accumulated excessive cAMP and elaborated appressoria on non-inductive surfaces, suggesting that Rgs1 regulates MagA during pathogenesis. Rgs1 was also found to negatively regulate the Gαi subunit MagB during asexual development. Deficiency of MAGB suppressed the hyper-conidiation defect in RGS1-deletion strain, whereas magBG183S and magBQ204L mutants produced more conidia, similar to the RGS1-deletion strain. Rgs1 physically interacted with GDP·AlF4−-activated forms of MagA, MagB and MagC (a GαII subunit). Thus, Rgs1 serves as a negative regulator of all Gα subunits in Magnaporthe and controls important developmental events during asexual and pathogenic development. PMID:17255942

  2. Rgs1 regulates multiple Galpha subunits in Magnaporthe pathogenesis, asexual growth and thigmotropism.

    Science.gov (United States)

    Liu, Hao; Suresh, Angayarkanni; Willard, Francis S; Siderovski, David P; Lu, Shen; Naqvi, Naweed I

    2007-02-07

    Regulators of G-protein signaling (RGS proteins) negatively regulate heterotrimeric G-protein cascades that enable eukaryotic cells to perceive and respond to external stimuli. The rice-blast fungus Magnaporthe grisea forms specialized infection structures called appressoria in response to inductive surface cues. We isolated Magnaporthe RGS1 in a screen for mutants that form precocious appressoria on non-inductive surfaces. We report that a thigmotropic cue is necessary for initiating appressoria and for accumulating cAMP. Similar to an RGS1-deletion strain, magA(G187S) (RGS-insensitive Galpha(s)) and magA(Q208L) (GTPase-dead) mutants accumulated excessive cAMP and elaborated appressoria on non-inductive surfaces, suggesting that Rgs1 regulates MagA during pathogenesis. Rgs1 was also found to negatively regulate the Galpha(i) subunit MagB during asexual development. Deficiency of MAGB suppressed the hyper-conidiation defect in RGS1-deletion strain, whereas magB(G183S) and magB(Q204L) mutants produced more conidia, similar to the RGS1-deletion strain. Rgs1 physically interacted with GDP.AlF(4)(-)-activated forms of MagA, MagB and MagC (a Galpha(II) subunit). Thus, Rgs1 serves as a negative regulator of all Galpha subunits in Magnaporthe and controls important developmental events during asexual and pathogenic development.

  3. HoloTrap: Interactive hologram design for multiple dynamic optical trapping

    Science.gov (United States)

    Pleguezuelos, E.; Carnicer, A.; Andilla, J.; Martín-Badosa, E.; Montes-Usategui, M.

    2007-06-01

    This work presents an application that generates real-time holograms to be displayed on a holographic optical tweezers setup; a technique that allows the manipulation of particles in the range from micrometres to nanometres. The software is written in Java, and uses random binary masks to generate the holograms. It allows customization of several parameters that are dependent on the experimental setup, such as the specific characteristics of the device displaying the hologram, or the presence of aberrations. We evaluate the software's performance and conclude that real-time interaction is achieved. We give our experimental results from manipulating 5 μm microspheres using the program. Program summaryTitle of program: HoloTrap Catalogue identifier:ADZB_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/ADZB_v1_0 Program obtainable from: CPC Program Library, Queen's University of Belfast, N. Ireland Computer for which the program is designed and others on which it has been tested: General computer Operating systems or monitors under which the program has been tested: Windows, Linux Programming language used: Java Memory required to execute with typical data: up to 34 MB including the Java Virtual Machine No. of bits in a word: 8 bits No. of processors used: 1 Has the code been vectorized or parallelized?: No No. of lines in distributed program, including test data, etc.: 471 145 No. of bytes in distributed program, including test data, etc.: 1 141 457 Distribution format: tar.gz Nature of physical problem: To calculate and display holograms for generating multiple and dynamic optical tweezers to be reconfigured interactively. Method of solution: Fast random binary mask for the simultaneous codification of multiple phase functions into a phase modulation device. Typical running time: Up to 10 frames per second Unusual features of the program: None References: The method for calculating holograms can be found in [M. Montes-Usategui, E. Pleguezuelos, J. Andilla

  4. Stressing Escherichia coli to educate students about research: A CURE to investigate multiple levels of gene regulation.

    Science.gov (United States)

    McDonough, Janet; Goudsouzian, Lara K; Papaj, Agllai; Maceli, Ashley R; Klepac-Ceraj, Vanja; Peterson, Celeste N

    2017-09-01

    Course-based undergraduate research experiences (CUREs) have been shown to increase student retention and learning in the biological sciences. Most CURES cover only one aspect of gene regulation, such as transcriptional control. Here we present a new inquiry-based lab that engages understanding of gene expression from multiple perspectives. Students carry out a forward genetic screen to identify regulators of the stationary phase master regulator RpoS in the model organism Escherichia coli and then use a series of reporter fusions to determine if the regulation is at the level of transcription or the post-transcription level. This easy-to-implement course has been run both as a 9-week long project and a condensed 5-6 week version in three different schools and types of courses. A majority of the genes found in the screen are novel, thus giving students the opportunity to contribute to original findings to the field. Assessments of this CURE show student gains in learning in many knowledge areas. In addition, attitudinal surveys suggest the students are enthusiastic about the screen and their learning about gene regulation. In summary, this lab would be an appropriate addition to an intermediate or advanced level Molecular Biology, Genetics, or Microbiology curriculum. © 2017 by The International Union of Biochemistry and Molecular Biology, 45(5):449-458, 2017. © 2017 The International Union of Biochemistry and Molecular Biology.

  5. Probabilistic Evaluation of Anthropogenic Regulations In a Vegetated River Channel Using a Vegetation Dynamics Modeling

    Science.gov (United States)

    Miyamoto, Hitoshi

    2015-04-01

    Vegetation overgrowth in fluvial floodplains, gravel beds, and sand bars has been a serious engineering problem for riparian management in Japan. From the viewpoints of flood control and ecological conservation, it would be necessary to predict the vegetation dynamics accurately for long-term duration. In this research, we have developed a stochastic model for predicting the vegetation dynamics in fluvial floodplains with emphasis on the interaction with flood impacts. The model consists of the following four components: (i) long-term stochastic behavior of flow discharge, (ii) hydrodynamics in a channel with floodplain vegetation, (iii) variation of riverbed topography, and (iv) vegetation dynamics on floodplains. In the vegetation dynamics model, the flood discharge (i) is stochastically simulated using a filtered Poisson process, one of the conventional approaches in hydrological time-series generation. The component for vegetation dynamics (iv) includes the effects of tree growth, mortality by floods, and infant tree recruitment. Vegetation condition has been observed mainly before and after floods since 2008 at a field site located between 23-24 km from the river mouth in Kako River, Japan. The Kako River has the catchment area of 1,730 km2 and the main channel length of 96 km. This site is one of the vegetation overgrowth sites in the Kako River floodplains. The predominant tree species are willows and bamboos. In the field survey, the position, trunk diameter and height of each tree as well as the riverbed materials were measured after several flood events to investigate their impacts on the floodplain vegetation community. This presentation tries to examine effects of anthropogenic river regulations, i.e., thinning and cutting-down, in the vegetated channel in Kako River by using the vegetation dynamics model. Sensitivity of both the flood water level and the vegetation status in the channel is statistically evaluated in terms of the different cutting

  6. The demography of climate-driven and density-regulated population dynamics in a perennial plant

    DEFF Research Database (Denmark)

    Dahlgren, Johan; Bengstsson, Karin; Ehrlén, Johan

    2016-01-01

    Identifying the internal and external drivers of population dynamics is a key objective in ecology, currently accentuated by the need to forecast the effects of climate change on species distributions and abundances. The interplay between environmental and density effects is one particularly...... important aspect of such forecasts. We examined the simultaneous impact of climate and intraspecific density on vital rates of the dwarf shrub Fumana procumbens over 20 yr, using generalized additive mixed models. We then analyzed effects on population dynamics using integral projection models...... to be driven solely by the environment can overestimate extinction risks if there is density dependence. We conclude that density regulation can dampen effects of climate change on Fumana population size, and discuss the need to quantify density dependence in predictions of population responses...

  7. Dynamic regulation of fatty acid pools for improved production of fatty alcohols in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Teixeira, Paulo Goncalves; Ferreira, Raphael; Zhou, Yongjin J.

    2017-01-01

    loss of precursors that compromises the process yield. In the present study, we aimed for dynamic expression of the fatty acyl-CoA synthetase gene FAA1 to regulate FFA and acyl-CoA pools in order to improve fatty alcohol production yields. Results: We analyzed the metabolite dynamics of a faa1 Delta...... faa4 Delta strain constitutively expressing a carboxylic acid reductase from Mycobacterium marinum (MmCAR) and an endogenous alcohol dehydrogenase (Adh5) for in vivo production of fatty alcohols from FFAs. We observed production of fatty acids and fatty alcohols with different rates leading to high...... levels of FFAs not being converted to the final product. To address the issue, we expressed the MmCAR + Adh5 pathway together with a fatty acyl-CoA reductase from Marinobacter aquaeolei to enable fatty alcohol production simultaneously from FFA and acyl-CoA, respectively. Then, we expressed FAA1 under...

  8. CSPGs inhibit axon branching by impairing mitochondria-dependent regulation of actin dynamics and axonal translation.

    Science.gov (United States)

    Sainath, Rajiv; Ketschek, Andrea; Grandi, Leah; Gallo, Gianluca

    2017-04-01

    Chondroitin sulfate proteoglycans (CSPGs) inhibit the formation of axon collateral branches. The regulation of the axonal cytoskeleton and mitochondria are important components of the mechanism of branching. Actin-dependent axonal plasticity, reflected in the dynamics of axonal actin patches and filopodia, is greatest along segments of the axon populated by mitochondria. It is reported that CSPGs partially depolarize the membrane potential of axonal mitochondria, which impairs the dynamics of the axonal actin cytoskeleton and decreases the formation and duration of axonal filopodia, the first steps in the mechanism of branching. The effects of CSPGs on actin cytoskeletal dynamics are specific to axon segments populated by mitochondria. In contrast, CSPGs do not affect the microtubule content of axons, or the localization of microtubules into axonal filopodia, a required step in the mechanism of branch formation. It is also reported that CSPGs decrease the mitochondria-dependent axonal translation of cortactin, an actin associated protein involved in branching. Finally, the inhibitory effects of CSPGs on axon branching, actin cytoskeletal dynamics and the axonal translation of cortactin are reversed by culturing neurons with acetyl-l-carnitine, which promotes mitochondrial respiration. Collectively these data indicate that CSPGs impair mitochondrial function in axons, an effect which contributes to the inhibition of axon branching. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 419-437, 2017. © 2016 Wiley Periodicals, Inc.

  9. Tissue organization by cadherin adhesion molecules: dynamic molecular and cellular mechanisms of morphogenetic regulation

    Science.gov (United States)

    Niessen, Carien M.; Leckband, Deborah; Yap, Alpha S.

    2013-01-01

    This review addresses the cellular and molecular mechanisms of cadherin-based tissue morphogenesis. Tissue physiology is profoundly influenced by the distinctive organizations of cells in organs and tissues. In metazoa, adhesion receptors of the classical cadherin family play important roles in establishing and maintaining such tissue organization. Indeed, it is apparent that cadherins participate in a range of morphogenetic events that range from support of tissue integrity to dynamic cellular rearrangements. A comprehensive understanding of cadherin-based morphogenesis must then define the molecular and cellular mechanisms that support these distinct cadherin biologies. Here we focus on four key mechanistic elements: the molecular basis for adhesion through cadherin ectodomains; the regulation of cadherin expression at the cell surface; cooperation between cadherins and the actin cytoskeleton; and regulation by cell signaling. We discuss current progress and outline issues for further research in these fields. PMID:21527735

  10. Cognitive radio policy and regulation techno-economic studies to facilitate dynamic spectrum access

    CERN Document Server

    Holland, Oliver

    2014-01-01

    This book offers a timely reflection on how the proliferation of advanced wireless communications technologies, particularly cognitive radio (CR) can be enabled by thoroughly-considered policy and appropriate regulation. It looks at the prospects of CR from the divergent standpoints of technological development and economic market reality. The book provides a broad survey of various techno-economic and policy aspects of CR development, and provides the reader with an understanding of the complexities involved as well as a toolbox of possible solutions to enable the evolutionary leap towards successful implementation of disruptive CR technology or indeed any other novel wireless technologies. Cognitive Radio Policy and Regulation showcases the original ideas and concepts introduced into the field of CR and dynamic spectrum access policy over nearly four years of work within COST Action IC0905 TERRA, a think-tank with participants from more than 20 countries. The book’s subject matter includes: • deploymen...

  11. Regional hippocampal vulnerability in early multiple sclerosis: Dynamic pathological spreading from dentate gyrus to CA1.

    Science.gov (United States)

    Planche, Vincent; Koubiyr, Ismail; Romero, José E; Manjon, José V; Coupé, Pierrick; Deloire, Mathilde; Dousset, Vincent; Brochet, Bruno; Ruet, Aurélie; Tourdias, Thomas

    2018-04-01

    Whether hippocampal subfields are differentially vulnerable at the earliest stages of multiple sclerosis (MS) and how this impacts memory performance is a current topic of debate. We prospectively included 56 persons with clinically isolated syndrome (CIS) suggestive of MS in a 1-year longitudinal study, together with 55 matched healthy controls at baseline. Participants were tested for memory performance and scanned with 3 T MRI to assess the volume of 5 distinct hippocampal subfields using automatic segmentation techniques. At baseline, CA4/dentate gyrus was the only hippocampal subfield with a volume significantly smaller than controls (p < .01). After one year, CA4/dentate gyrus atrophy worsened (-6.4%, p < .0001) and significant CA1 atrophy appeared (both in the stratum-pyramidale and the stratum radiatum-lacunosum-moleculare, -5.6%, p < .001 and -6.2%, p < .01, respectively). CA4/dentate gyrus volume at baseline predicted CA1 volume one year after CIS (R 2  = 0.44 to 0.47, p < .001, with age, T2 lesion-load, and global brain atrophy as covariates). The volume of CA4/dentate gyrus at baseline was associated with MS diagnosis during follow-up, independently of T2-lesion load and demographic variables (p < .05). Whereas CA4/dentate gyrus volume was not correlated with memory scores at baseline, CA1 atrophy was an independent correlate of episodic verbal memory performance one year after CIS (ß = 0.87, p < .05). The hippocampal degenerative process spread from dentate gyrus to CA1 at the earliest stage of MS. This dynamic vulnerability is associated with MS diagnosis after CIS and will ultimately impact hippocampal-dependent memory performance. © 2018 Wiley Periodicals, Inc.

  12. Engineering 1-Alkene Biosynthesis and Secretion by Dynamic Regulation in Yeast

    DEFF Research Database (Denmark)

    Zhou, Yongjin J.; Hu, Yating; Zhu, Zhiwei

    2018-01-01

    product secretion. Here, we engineered the budding yeast Saccharomyces cerevisiae to produce and secrete 1-alkenes by manipulation of the fatty acid metabolism, enzyme selection, engineering the electron transfer system and expressing a transporter. Furthermore, we implemented a dynamic regulation...... strategy to control the expression of membrane enzyme and 1-alkene production and cell growth by relieving the possible toxicity of overexpressed membrane proteins. With these efforts, the engineered yeast cell factory produced 35.3 mg/L 1-alkenes with more than 80% being secreted. This represents a 10...

  13. Multiple steady states, limit cycles and chaotic attractors in evolutionary games with Logit Dynamics

    NARCIS (Netherlands)

    Hommes, C.H.; Ochea, M.I.

    2010-01-01

    This paper investigates, by means of simple, three and four strategy games, the occurrence of periodic and chaotic behaviour in a smooth version of the Best Response Dynamics, the Logit Dynamics. The main finding is that, unlike Replicator Dynamics, generic Hopf bifurcation and thus, stable limit

  14. Quantitative analysis of proteome and lipidome dynamics reveals functional regulation of global lipid metabolism.

    Science.gov (United States)

    Casanovas, Albert; Sprenger, Richard R; Tarasov, Kirill; Ruckerbauer, David E; Hannibal-Bach, Hans Kristian; Zanghellini, Jürgen; Jensen, Ole N; Ejsing, Christer S

    2015-03-19

    Elucidating how and to what extent lipid metabolism is remodeled under changing conditions is essential for understanding cellular physiology. Here, we analyzed proteome and lipidome dynamics to investigate how regulation of lipid metabolism at the global scale supports remodeling of cellular architecture and processes during physiological adaptations in yeast. Our results reveal that activation of cardiolipin synthesis and remodeling supports mitochondrial biogenesis in the transition from fermentative to respiratory metabolism, that down-regulation of de novo sterol synthesis machinery prompts differential turnover of lipid droplet-associated triacylglycerols and sterol esters during respiratory growth, that sphingolipid metabolism is regulated in a previously unrecognized growth stage-specific manner, and that endogenous synthesis of unsaturated fatty acids constitutes an in vivo upstream activator of peroxisomal biogenesis, via the heterodimeric Oaf1/Pip2 transcription factor. Our work demonstrates the pivotal role of lipid metabolism in adaptive processes and provides a resource to investigate its regulation at the cellular level. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Novel Regulation of Ski Protein Stability and Endosomal Sorting by Actin Cytoskeleton Dynamics in Hepatocytes*

    Science.gov (United States)

    Vázquez-Victorio, Genaro; Caligaris, Cassandre; Del Valle-Espinosa, Eugenio; Sosa-Garrocho, Marcela; González-Arenas, Nelly R.; Reyes-Cruz, Guadalupe; Briones-Orta, Marco A.; Macías-Silva, Marina

    2015-01-01

    TGF-β-induced antimitotic signals are highly regulated during cell proliferation under normal and pathological conditions, such as liver regeneration and cancer. Up-regulation of the transcriptional cofactors Ski and SnoN during liver regeneration may favor hepatocyte proliferation by inhibiting TGF-β signals. In this study, we found a novel mechanism that regulates Ski protein stability through TGF-β and G protein-coupled receptor (GPCR) signaling. Ski protein is distributed between the nucleus and cytoplasm of normal hepatocytes, and the molecular mechanisms controlling Ski protein stability involve the participation of actin cytoskeleton dynamics. Cytoplasmic Ski is partially associated with actin and localized in cholesterol-rich vesicles. Ski protein stability is decreased by TGF-β/Smads, GPCR/Rho signals, and actin polymerization, whereas GPCR/cAMP signals and actin depolymerization promote Ski protein stability. In conclusion, TGF-β and GPCR signals differentially regulate Ski protein stability and sorting in hepatocytes, and this cross-talk may occur during liver regeneration. PMID:25561741

  16. Novel regulation of Ski protein stability and endosomal sorting by actin cytoskeleton dynamics in hepatocytes.

    Science.gov (United States)

    Vázquez-Victorio, Genaro; Caligaris, Cassandre; Del Valle-Espinosa, Eugenio; Sosa-Garrocho, Marcela; González-Arenas, Nelly R; Reyes-Cruz, Guadalupe; Briones-Orta, Marco A; Macías-Silva, Marina

    2015-02-13

    TGF-β-induced antimitotic signals are highly regulated during cell proliferation under normal and pathological conditions, such as liver regeneration and cancer. Up-regulation of the transcriptional cofactors Ski and SnoN during liver regeneration may favor hepatocyte proliferation by inhibiting TGF-β signals. In this study, we found a novel mechanism that regulates Ski protein stability through TGF-β and G protein-coupled receptor (GPCR) signaling. Ski protein is distributed between the nucleus and cytoplasm of normal hepatocytes, and the molecular mechanisms controlling Ski protein stability involve the participation of actin cytoskeleton dynamics. Cytoplasmic Ski is partially associated with actin and localized in cholesterol-rich vesicles. Ski protein stability is decreased by TGF-β/Smads, GPCR/Rho signals, and actin polymerization, whereas GPCR/cAMP signals and actin depolymerization promote Ski protein stability. In conclusion, TGF-β and GPCR signals differentially regulate Ski protein stability and sorting in hepatocytes, and this cross-talk may occur during liver regeneration. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. Severity of Children's ADHD Symptoms and Parenting Stress: A Multiple Mediation Model of Self-Regulation

    Science.gov (United States)

    Graziano, Paulo A.; McNamara, Joseph P.; Geffken, Gary R.; Reid, Adam

    2011-01-01

    The goal of the current study was to determine the extent to which the perceived self-regulation deficits across behavioral, cognitive, and emotional domains seen in children with ADHD explain the association between the severity of ADHD symptoms and parenting stress. Participants for this study included 80 children (mean age = 10 years, 9 months)…

  18. Estrogens regulate the hepatic effects of growth hormone, a hormonal interplay with multiple fates

    DEFF Research Database (Denmark)

    Fernández-Pérez, Leandro; Guerra, Borja; Díaz-Chico, Juan C

    2013-01-01

    The liver responds to estrogens and growth hormone (GH) which are critical regulators of body growth, gender-related hepatic functions, and intermediate metabolism. The effects of estrogens on liver can be direct, through the direct actions of hepatic ER, or indirect, which include the crosstalk...

  19. Systems analysis of multiple regulator perturbations allows discovery of virulence factors in Salmonella

    Directory of Open Access Journals (Sweden)

    Heffron Fred

    2011-06-01

    Full Text Available Abstract Background Systemic bacterial infections are highly regulated and complex processes that are orchestrated by numerous virulence factors. Genes that are coordinately controlled by the set of regulators required for systemic infection are potentially required for pathogenicity. Results In this study we present a systems biology approach in which sample-matched multi-omic measurements of fourteen virulence-essential regulator mutants were coupled with computational network analysis to efficiently identify Salmonella virulence factors. Immunoblot experiments verified network-predicted virulence factors and a subset was determined to be secreted into the host cytoplasm, suggesting that they are virulence factors directly interacting with host cellular components. Two of these, SrfN and PagK2, were required for full mouse virulence and were shown to be translocated independent of either of the type III secretion systems in Salmonella or the type III injectisome-related flagellar mechanism. Conclusions Integrating multi-omic datasets from Salmonella mutants lacking virulence regulators not only identified novel virulence factors but also defined a new class of translocated effectors involved in pathogenesis. The success of this strategy at discovery of known and novel virulence factors suggests that the approach may have applicability for other bacterial pathogens.

  20. Insights into the regulation of bacteriophage endolysin: multiple means to the same end.

    Science.gov (United States)

    Pohane, Amol Arunrao; Jain, Vikas

    2015-12-01

    Antibiotics are the molecules of choice to treat bacterial infections. However, because of the rapid emergence of drug-resistant bacteria, alternative modes of combating infections are being envisaged. Bacteriophages, which infect and lyse bacterial cells, may function as effective antimicrobial agents. Most bacteriophages produce their own peptidoglycan hydrolase called endolysin or lysin, which breaks down the cell wall of bacteria and aids in the release of newly assembled virions. Here, we discuss several findings that help us in understanding how endolysins are regulated. We observe that there is no common mechanism that is followed in all cases. Many different modes of activity regulation have been observed in endolysins, including regulation of protein expression, translocation across the cell membrane and post-translational modifications. These processes not only demonstrate how endolysins are made dependent on other accessory proteins and non-protein factors for their synthesis, translocation across the cytoplasmic membrane and activity, but also show how autoregulation helps in maintaining the enzyme in an inactive form. Various regulatory mechanisms that are discussed are particularly applicable to endolysins. Nevertheless, a detailed study of these methods opens new avenues of investigation in the area of protein translocation systems and the novel ways of enzyme activation and regulation in bacteria.

  1. Systems analysis of multiple regulator perturbations allows discovery of virulence factors in Salmonella

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Hyunjin; Ansong, Charles; McDermott, Jason E.; Gritsenko, Marina A.; Smith, Richard D.; Heffron, Fred; Adkins, Joshua N.

    2011-06-28

    Background: Systemic bacterial infections are highly regulated and complex processes that are orchestrated by numerous virulence factors. Genes that are coordinately controlled by the set of regulators required for systemic infection are potentially required for pathogenicity. Results: In this study we present a systems biology approach in which sample-matched multi-omic measurements of fourteen virulence-essential regulator mutants were coupled with computational network analysis to efficiently identify Salmonella virulence factors. Immunoblot experiments verified network-predicted virulence factors and a subset was determined to be secreted into the host cytoplasm, suggesting that they are virulence factors directly interacting with host cellular components. Two of these, SrfN and PagK2, were required for full mouse virulence and were shown to be translocated independent of either of the type III secretion systems in Salmonella or the type III injectisome-related flagellar mechanism. Conclusions: Integrating multi-omic datasets from Salmonella mutants lacking virulence regulators not only identified novel virulence factors but also defined a new class of translocated effectors involved in pathogenesis. The success of this strategy at discovery of known and novel virulence factors suggests that the approach may have applicability for other bacterial pathogens.

  2. Dynamic modeling and hierarchical compound control of a novel 2-DOF flexible parallel manipulator with multiple actuation modes

    Science.gov (United States)

    Liang, Dong; Song, Yimin; Sun, Tao; Jin, Xueying

    2018-03-01

    This paper addresses the problem of rigid-flexible coupling dynamic modeling and active control of a novel flexible parallel manipulator (PM) with multiple actuation modes. Firstly, based on the flexible multi-body dynamics theory, the rigid-flexible coupling dynamic model (RFDM) of system is developed by virtue of the augmented Lagrangian multipliers approach. For completeness, the mathematical models of permanent magnet synchronous motor (PMSM) and piezoelectric transducer (PZT) are further established and integrated with the RFDM of mechanical system to formulate the electromechanical coupling dynamic model (ECDM). To achieve the trajectory tracking and vibration suppression, a hierarchical compound control strategy is presented. Within this control strategy, the proportional-differential (PD) feedback controller is employed to realize the trajectory tracking of end-effector, while the strain and strain rate feedback (SSRF) controller is developed to restrain the vibration of the flexible links using PZT. Furthermore, the stability of the control algorithm is demonstrated based on the Lyapunov stability theory. Finally, two simulation case studies are performed to illustrate the effectiveness of the proposed approach. The results indicate that, under the redundant actuation mode, the hierarchical compound control strategy can guarantee the flexible PM achieves singularity-free motion and vibration attenuation within task workspace simultaneously. The systematic methodology proposed in this study can be conveniently extended for the dynamic modeling and efficient controller design of other flexible PMs, especially the emerging ones with multiple actuation modes.

  3. Use of multiple picosecond high-mass molecular dynamics simulations to predict crystallographic B-factors of folded globular proteins

    Directory of Open Access Journals (Sweden)

    Yuan-Ping Pang

    2016-09-01

    Full Text Available Predicting crystallographic B-factors of a protein from a conventional molecular dynamics simulation is challenging, in part because the B-factors calculated through sampling the atomic positional fluctuations in a picosecond molecular dynamics simulation are unreliable, and the sampling of a longer simulation yields overly large root mean square deviations between calculated and experimental B-factors. This article reports improved B-factor prediction achieved by sampling the atomic positional fluctuations in multiple picosecond molecular dynamics simulations that use uniformly increased atomic masses by 100-fold to increase time resolution. Using the third immunoglobulin-binding domain of protein G, bovine pancreatic trypsin inhibitor, ubiquitin, and lysozyme as model systems, the B-factor root mean square deviations (mean ± standard error of these proteins were 3.1 ± 0.2–9 ± 1 Å2 for Cα and 7.3 ± 0.9–9.6 ± 0.2 Å2 for Cγ, when the sampling was done for each of these proteins over 20 distinct, independent, and 50-picosecond high-mass molecular dynamics simulations with AMBER forcefield FF12MC or FF14SB. These results suggest that sampling the atomic positional fluctuations in multiple picosecond high-mass molecular dynamics simulations may be conducive to a priori prediction of crystallographic B-factors of a folded globular protein.

  4. RhoGDI: multiple functions in the regulation of Rho family GTPase activities

    DEFF Research Database (Denmark)

    Dovas, Athanassios; Couchman, John R

    2005-01-01

    insight as to how RhoGDI exerts its effects on nucleotide binding, the membrane association-dissociation cycling of the GTPase and how these activities are controlled. Despite the initial negative roles attributed to RhoGDI, recent evidence has come to suggest that it may also act as a positive regulator...... and the importance of the particular membrane microenvironment that represents the site of action for GTPases. All these results point to a wider role for RhoGDI than initially perceived, making it a binding partner that can tightly control Rho GTPases, but which also allows them to reach their full spectrum......RhoGDI (Rho GDP-dissociation inhibitor) was identified as a down-regulator of Rho family GTPases typified by its ability to prevent nucleotide exchange and membrane association. Structural studies on GTPase-RhoGDI complexes, in combination with biochemical and cell biological results, have provided...

  5. Cell-cycle regulation in green algae dividing by multiple fission

    Czech Academy of Sciences Publication Activity Database

    Bišová, Kateřina; Zachleder, Vilém

    2014-01-01

    Roč. 65, č. 10 (2014), s. 2585-2602 ISSN 0022-0957 R&D Projects: GA ČR M200201205; GA MŠk LH12145 Grant - others:Centre for Algal Biotechnologies (Algatech)(CZ) CZ.1.05/2.1.00/03.0110 Institutional support: RVO:61388971 Keywords : cell cycle * regulation * growth * light Subject RIV: EE - Microbiology, Virology Impact factor: 5.526, year: 2014

  6. Dynamic hubs show competitive and static hubs non-competitive regulation of their interaction partners.

    Directory of Open Access Journals (Sweden)

    Apurv Goel

    Full Text Available Date hub proteins have 1 or 2 interaction interfaces but many interaction partners. This raises the question of whether all partner proteins compete for the interaction interface of the hub or if the cell carefully regulates aspects of this process? Here, we have used real-time rendering of protein interaction networks to analyse the interactions of all the 1 or 2 interface hubs of Saccharomyces cerevisiae during the cell cycle. By integrating previously determined structural and gene expression data, and visually hiding the nodes (proteins and their edges (interactions during their troughs of expression, we predict when interactions of hubs and their partners are likely to exist. This revealed that 20 out of all 36 one- or two- interface hubs in the yeast interactome fell within two main groups. The first was dynamic hubs with static partners, which can be considered as 'competitive hubs'. Their interaction partners will compete for the interaction interface of the hub and the success of any interaction will be dictated by the kinetics of interaction (abundance and affinity and subcellular localisation. The second was static hubs with dynamic partners, which we term 'non-competitive hubs'. Regulatory mechanisms are finely tuned to lessen the presence and/or effects of competition between the interaction partners of the hub. It is possible that these regulatory processes may also be used by the cell for the regulation of other, non-cell cycle processes.

  7. Dynamic hubs show competitive and static hubs non-competitive regulation of their interaction partners.

    Science.gov (United States)

    Goel, Apurv; Wilkins, Marc R

    2012-01-01

    Date hub proteins have 1 or 2 interaction interfaces but many interaction partners. This raises the question of whether all partner proteins compete for the interaction interface of the hub or if the cell carefully regulates aspects of this process? Here, we have used real-time rendering of protein interaction networks to analyse the interactions of all the 1 or 2 interface hubs of Saccharomyces cerevisiae during the cell cycle. By integrating previously determined structural and gene expression data, and visually hiding the nodes (proteins) and their edges (interactions) during their troughs of expression, we predict when interactions of hubs and their partners are likely to exist. This revealed that 20 out of all 36 one- or two- interface hubs in the yeast interactome fell within two main groups. The first was dynamic hubs with static partners, which can be considered as 'competitive hubs'. Their interaction partners will compete for the interaction interface of the hub and the success of any interaction will be dictated by the kinetics of interaction (abundance and affinity) and subcellular localisation. The second was static hubs with dynamic partners, which we term 'non-competitive hubs'. Regulatory mechanisms are finely tuned to lessen the presence and/or effects of competition between the interaction partners of the hub. It is possible that these regulatory processes may also be used by the cell for the regulation of other, non-cell cycle processes.

  8. Caudal regulates the spatiotemporal dynamics of pair-rule waves in Tribolium.

    Directory of Open Access Journals (Sweden)

    Ezzat El-Sherif

    2014-10-01

    Full Text Available In the short-germ beetle Tribolium castaneum, waves of pair-rule gene expression propagate from the posterior end of the embryo towards the anterior and eventually freeze into stable stripes, partitioning the anterior-posterior axis into segments. Similar waves in vertebrates are assumed to arise due to the modulation of a molecular clock by a posterior-to-anterior frequency gradient. However, neither a molecular candidate nor a functional role has been identified to date for such a frequency gradient, either in vertebrates or elsewhere. Here we provide evidence that the posterior gradient of Tc-caudal expression regulates the oscillation frequency of pair-rule gene expression in Tribolium. We show this by analyzing the spatiotemporal dynamics of Tc-even-skipped expression in strong and mild knockdown of Tc-caudal, and by correlating the extension, level and slope of the Tc-caudal expression gradient to the spatiotemporal dynamics of Tc-even-skipped expression in wild type as well as in different RNAi knockdowns of Tc-caudal regulators. Further, we show that besides its absolute importance for stripe generation in the static phase of the Tribolium blastoderm, a frequency gradient might serve as a buffer against noise during axis elongation phase in Tribolium as well as vertebrates. Our results highlight the role of frequency gradients in pattern formation.

  9. ADAMTS9-Regulated Pericellular Matrix Dynamics Governs Focal Adhesion-Dependent Smooth Muscle Differentiation

    Directory of Open Access Journals (Sweden)

    Timothy J. Mead

    2018-04-01

    Full Text Available Summary: Focal adhesions anchor cells to extracellular matrix (ECM and direct assembly of a pre-stressed actin cytoskeleton. They act as a cellular sensor and regulator, linking ECM to the nucleus. Here, we identify proteolytic turnover of the anti-adhesive proteoglycan versican as a requirement for maintenance of smooth muscle cell (SMC focal adhesions. Using conditional deletion in mice, we show that ADAMTS9, a secreted metalloprotease, is required for myometrial activation during late gestation and for parturition. Through knockdown of ADAMTS9 in uterine SMC, and manipulation of pericellular versican via knockdown or proteolysis, we demonstrate that regulated pericellular matrix dynamics is essential for focal adhesion maintenance. By influencing focal adhesion formation, pericellular versican acts upstream of cytoskeletal assembly and SMC differentiation. Thus, pericellular versican proteolysis by ADAMTS9 balances pro- and anti-adhesive forces to maintain an SMC phenotype, providing a concrete example of the dynamic reciprocity of cells and their ECM. : Mead et al. identify a proteolytic mechanism that actively maintains a pericellular microenvironment conducive to uterine smooth muscle activation prior to parturition. They show that pericellular matrix proteolysis by the secreted metalloprotease ADAMTS9 is crucial for maintenance of focal adhesions in uterine smooth muscle cells, and its absence impairs parturition. Keywords: metalloprotease, extracellular matrix, smooth muscle, proteoglycan, myometrium, parturition, uterus, focal adhesion, proteolysis, interference reflection microscopy

  10. Muscle lim protein isoform negatively regulates striated muscle actin dynamics and differentiation.

    Science.gov (United States)

    Vafiadaki, Elizabeth; Arvanitis, Demetrios A; Papalouka, Vasiliki; Terzis, Gerasimos; Roumeliotis, Theodoros I; Spengos, Konstantinos; Garbis, Spiros D; Manta, Panagiota; Kranias, Evangelia G; Sanoudou, Despina

    2014-07-01

    Muscle lim protein (MLP) has emerged as a critical regulator of striated muscle physiology and pathophysiology. Mutations in cysteine and glycine-rich protein 3 (CSRP3), the gene encoding MLP, have been directly associated with human cardiomyopathies, whereas aberrant expression patterns are reported in human cardiac and skeletal muscle diseases. Increasing evidence suggests that MLP has an important role in both myogenic differentiation and myocyte cytoarchitecture, although the full spectrum of its intracellular roles has not been delineated. We report the discovery of an alternative splice variant of MLP, designated as MLP-b, showing distinct expression in neuromuscular disease and direct roles in actin dynamics and muscle differentiation. This novel isoform originates by alternative splicing of exons 3 and 4. At the protein level, it contains the N-terminus first half LIM domain of MLP and a unique sequence of 22 amino acids. Physiologically, it is expressed during early differentiation, whereas its overexpression reduces C2C12 differentiation and myotube formation. This may be mediated through its inhibition of MLP/cofilin-2-mediated F-actin dynamics. In differentiated striated muscles, MLP-b localizes to the sarcomeres and binds directly to Z-disc components, including α-actinin, T-cap and MLP. The findings of the present study unveil a novel player in muscle physiology and pathophysiology that is implicated in myogenesis as a negative regulator of myotube formation, as well as in differentiated striated muscles as a contributor to sarcomeric integrity. © 2014 FEBS.

  11. An integrated cell purification and genomics strategy reveals multiple regulators of pancreas development.

    Directory of Open Access Journals (Sweden)

    Cecil M Benitez

    2014-10-01

    Full Text Available The regulatory logic underlying global transcriptional programs controlling development of visceral organs like the pancreas remains undiscovered. Here, we profiled gene expression in 12 purified populations of fetal and adult pancreatic epithelial cells representing crucial progenitor cell subsets, and their endocrine or exocrine progeny. Using probabilistic models to decode the general programs organizing gene expression, we identified co-expressed gene sets in cell subsets that revealed patterns and processes governing progenitor cell development, lineage specification, and endocrine cell maturation. Purification of Neurog3 mutant cells and module network analysis linked established regulators such as Neurog3 to unrecognized gene targets and roles in pancreas development. Iterative module network analysis nominated and prioritized transcriptional regulators, including diabetes risk genes. Functional validation of a subset of candidate regulators with corresponding mutant mice revealed that the transcription factors Etv1, Prdm16, Runx1t1 and Bcl11a are essential for pancreas development. Our integrated approach provides a unique framework for identifying regulatory genes and functional gene sets underlying pancreas development and associated diseases such as diabetes mellitus.

  12. MiR-155 Enhances Insulin Sensitivity by Coordinated Regulation of Multiple Genes in Mice.

    Directory of Open Access Journals (Sweden)

    Xiaolin Lin

    2016-10-01

    Full Text Available miR-155 plays critical roles in numerous physiological and pathological processes, however, its function in the regulation of blood glucose homeostasis and insulin sensitivity and underlying mechanisms remain unknown. Here, we reveal that miR-155 levels are downregulated in serum from type 2 diabetes (T2D patients, suggesting that miR-155 might be involved in blood glucose control and diabetes. Gain-of-function and loss-of-function studies in mice demonstrate that miR-155 has no effects on the pancreatic β-cell proliferation and function. Global transgenic overexpression of miR-155 in mice leads to hypoglycaemia, improved glucose tolerance and insulin sensitivity. Conversely, miR-155 deficiency in mice causes hyperglycemia, impaired glucose tolerance and insulin resistance. In addition, consistent with a positive regulatory role of miR-155 in glucose metabolism, miR-155 positively modulates glucose uptake in all cell types examined, while mice overexpressing miR-155 transgene show enhanced glycolysis, and insulin-stimulated AKT and IRS-1 phosphorylation in liver, adipose tissue or skeletal muscle. Furthermore, we reveal these aforementioned phenomena occur, at least partially, through miR-155-mediated repression of important negative regulators (i.e. C/EBPβ, HDAC4 and SOCS1 of insulin signaling. Taken together, these findings demonstrate, for the first time, that miR-155 is a positive regulator of insulin sensitivity with potential applications for diabetes treatment.

  13. Multiple regulations of Keap1/Nrf2 system by dietary phytochemicals.

    Science.gov (United States)

    Qin, Si; Hou, De-Xing

    2016-08-01

    Keap1/Nrf2 system plays a critical role on cellular protection by regulating many antioxidant and detoxification enzyme genes through the antioxidant response element (ARE). Thus, it must work constantly to prevent the accumulation of reactive oxygen species (ROS) because excess ROS are associated with many diseases such as cancer, cardiovascular complications, inflammation, and neurodegeneration. Dietary phytochemicals widely distributing in fruits and vegetables have been considered to possess cancer chemopreventive potential through the induction of Keap1/Nrf2 system-mediated antioxidant and detoxification enzymes in a variety of manners. The data are extensive and are not well classified on the molecular mechanisms. In this review, we first briefly introduce the current knowledge on Keap1/Nrf2 system regulation including Keap1-dependent and Keap1-independent cascades, and epigenetic pathway. Then, we summarize the molecular targets of Keap1/Nrf2 system by dietary phytochemicals, and finally review the crosstalk between Keap1/Nrf2 system and other cellular signaling pathways to regulate diverse chronic diseases by dietary phytochemicals. These comprehensive data will help us to understand the potential effects of dietary phytochemicals on the prevention of chronic diseases and maintenance of human health. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Estrogens regulate the hepatic effects of Growth Hormone, a hormonal interplay with multiple fates

    Directory of Open Access Journals (Sweden)

    Leandro eFernandez-Perez

    2013-06-01

    Full Text Available The liver responds to estrogens and GH which are critical regulators of body growth, gender-related hepatic functions, and intermediate metabolism. The effects of estrogens on liver can be direct, through the direct actions of hepatic ER, or indirect, which include the crosstalk with endocrine, metabolic, and sex-differentiated functions of GH. Most previous studies have been focused on the influence of estrogens on pituitary GH secretion, which has a great impact on hepatic transcriptional regulation. However, there is strong evidence that estrogens can influence the GH-regulated endocrine and metabolic functions in the human liver by acting at the level of GHR-STAT5 signaling pathway. This cross-talk is relevant because the widespread exposition of estrogen or estrogen-related compounds in human. Therefore, GH or estrogen signaling deficiency as well as the influence of estrogens on GH biology can cause a dramatic impact in liver physiology during mammalian development and in adulthood. In this review, we will summarize the current status of the influence of estrogen on GH actions in liver. A better understanding of estrogen-GH interplay in liver will lead to improved therapy of children with growth disorders and of adults with GH deficiency.

  15. Cellular volume regulation and substrate stiffness modulate the detachment dynamics of adherent cells

    Science.gov (United States)

    Yang, Yuehua; Jiang, Hongyuan

    2018-03-01

    Quantitative characterizations of cell detachment are vital for understanding the fundamental mechanisms of cell adhesion. Experiments have found that cell detachment shows strong rate dependence, which is mostly attributed to the binding-unbinding kinetics of receptor-ligand bond. However, our recent study showed that the cellular volume regulation can significantly regulate the dynamics of adherent cell and cell detachment. How this cellular volume regulation contributes to the rate dependence of cell detachment remains elusive. Here, we systematically study the role of cellular volume regulation in the rate dependence of cell detachment by investigating the cell detachments of nonspecific adhesion and specific adhesion. We find that the cellular volume regulation and the bond kinetics dominate the rate dependence of cell detachment at different time scales. We further test the validity of the traditional Johnson-Kendall-Roberts (JKR) contact model and the detachment model developed by Wyart and Gennes et al (W-G model). When the cell volume is changeable, the JKR model is not appropriate for both the detachments of convex cells and concave cells. The W-G model is valid for the detachment of convex cells but is no longer applicable for the detachment of concave cells. Finally, we show that the rupture force of adherent cells is also highly sensitive to substrate stiffness, since an increase in substrate stiffness will lead to more associated bonds. These findings can provide insight into the critical role of cell volume in cell detachment and might have profound implications for other adhesion-related physiological processes.

  16. Dynamical and technological consequences of multiple isolas of steady states in a catalytic fluidised-bed reactor

    Directory of Open Access Journals (Sweden)

    Bizon Katarzyna

    2017-09-01

    Full Text Available Steady-state characteristics of a catalytic fluidised bed reactor and its dynamical consequences are analyzed. The occurrence of an untypical steady-state structure manifesting in a form of multiple isolas is described. A two-phase bubbling bed model is used for a quantitative description of the bed of catalyst. The influence of heat exchange intensity and a fluidisation ratio onto the generation of isolated solution branches is presented for two kinetic schemes. Dynamical consequences of the coexistence of such untypical branches of steady states are presented. The impact of linear growth of the fluidisation ratio and step change of the cooling medium temperature onto the desired product yield is analyzed. The results presented in this study confirm that the identification of a region of the occurrence of multiple isolas is important due to their strong impact both on the process start-up and its control.

  17. Murine Mesenchymal Stem Cell Commitment to Differentiation Is Regulated by Mitochondrial Dynamics.

    Science.gov (United States)

    Forni, Maria Fernanda; Peloggia, Julia; Trudeau, Kyle; Shirihai, Orian; Kowaltowski, Alicia J

    2016-03-01

    Mouse skin mesenchymal stem cells (msMSCs) are dermis CD105(+) CD90(+) CD73(+) CD29(+) CD34(-) mesodermal precursors which, after in vitro induction, undergo chondro, adipo, and osteogenesis. Extensive metabolic reconfiguration has been found to occur during differentiation, and the bioenergetic status of a cell is known to be dependent on the quality and abundance of the mitochondrial population, which may be regulated by fusion and fission. However, little is known regarding the impact of mitochondrial dynamics on the differentiation process. We addressed this knowledge gap by isolating MSCs from Swiss female mice, inducing these cells to differentiate into osteo, chondro, and adipocytes and measuring changes in mass, morphology, dynamics, and bioenergetics. Mitochondrial biogenesis was increased in adipogenesis, as evaluated through confocal microscopy, citrate synthase activity, and mtDNA content. The early steps of adipo and osteogenesis involved mitochondrial elongation, as well as increased expression of mitochondrial fusion proteins Mfn1 and 2. Chondrogenesis involved a fragmented mitochondrial phenotype, increased expression of fission proteins Drp1, Fis1, and 2, and enhanced mitophagy. These events were accompanied by profound bioenergetic alterations during the commitment period. Moreover, knockdown of Mfn2 in adipo and osteogenesis and the overexpression of a dominant negative form of Drp1 during chondrogenesis resulted in a loss of differentiation ability. Overall, we find that mitochondrial morphology and its regulating processes of fission/fusion are modulated early on during commitment, leading to alterations in the bioenergetic profile that are important for differentiation. We thus propose a central role for mitochondrial dynamics in the maintenance/commitment of mesenchymal stem cells. © 2015 AlphaMed Press.

  18. Improving fatty acids production by engineering dynamic pathway regulation and metabolic control

    Science.gov (United States)

    Xu, Peng; Li, Lingyun; Zhang, Fuming; Stephanopoulos, Gregory; Koffas, Mattheos

    2014-01-01

    Global energy demand and environmental concerns have stimulated increasing efforts to produce carbon-neutral fuels directly from renewable resources. Microbially derived aliphatic hydrocarbons, the petroleum-replica fuels, have emerged as promising alternatives to meet this goal. However, engineering metabolic pathways with high productivity and yield requires dynamic redistribution of cellular resources and optimal control of pathway expression. Here we report a genetically encoded metabolic switch that enables dynamic regulation of fatty acids (FA) biosynthesis in Escherichia coli. The engineered strains were able to dynamically compensate the critical enzymes involved in the supply and consumption of malonyl-CoA and efficiently redirect carbon flux toward FA biosynthesis. Implementation of this metabolic control resulted in an oscillatory malonyl-CoA pattern and a balanced metabolism between cell growth and product formation, yielding 15.7- and 2.1-fold improvement in FA titer compared with the wild-type strain and the strain carrying the uncontrolled metabolic pathway. This study provides a new paradigm in metabolic engineering to control and optimize metabolic pathways facilitating the high-yield production of other malonyl-CoA–derived compounds. PMID:25049420

  19. An experimental approach to identify dynamical models of transcriptional regulation in living cells

    Science.gov (United States)

    Fiore, G.; Menolascina, F.; di Bernardo, M.; di Bernardo, D.

    2013-06-01

    We describe an innovative experimental approach, and a proof of principle investigation, for the application of System Identification techniques to derive quantitative dynamical models of transcriptional regulation in living cells. Specifically, we constructed an experimental platform for System Identification based on a microfluidic device, a time-lapse microscope, and a set of automated syringes all controlled by a computer. The platform allows delivering a time-varying concentration of any molecule of interest to the cells trapped in the microfluidics device (input) and real-time monitoring of a fluorescent reporter protein (output) at a high sampling rate. We tested this platform on the GAL1 promoter in the yeast Saccharomyces cerevisiae driving expression of a green fluorescent protein (Gfp) fused to the GAL1 gene. We demonstrated that the System Identification platform enables accurate measurements of the input (sugars concentrations in the medium) and output (Gfp fluorescence intensity) signals, thus making it possible to apply System Identification techniques to obtain a quantitative dynamical model of the promoter. We explored and compared linear and nonlinear model structures in order to select the most appropriate to derive a quantitative model of the promoter dynamics. Our platform can be used to quickly obtain quantitative models of eukaryotic promoters, currently a complex and time-consuming process.

  20. Dynamics of peptidergic secretory granule transport are regulated by neuronal stimulation

    Directory of Open Access Journals (Sweden)

    Cowan Ann E

    2010-03-01

    Full Text Available Abstract Background Peptidergic neurons store and secrete the contents of large dense core vesicles (LDCVs from axon terminals and from dendrites. Secretion of peptides requires a highly regulated exocytotic mechanism, plus coordinated synthesis and transport of LDCVs to their sites of release. Although these trafficking events are critical to function, little is known regarding the dynamic behavior of LDCVs and the mechanisms by which their transport is regulated. Sensory neurons also package opiate receptors in peptide-containing LDCVs, which is thought to be important in pain sensation. Since peptide granules cannot be refilled locally after their contents are secreted, it is particularly important to understand how neurons support regulated release of peptides. Results A vector encoding soluble peptidylglycine α-hydroxylating monooxygenase fused to green fluorescent protein was constructed to address these questions in cultured primary peptidergic neurons of the trigeminal ganglion using time lapse confocal microscopy. The time course of release differs with secretagogue; the secretory response to depolarization with K+ is rapid and terminates within 15 minutes, while phorbol ester stimulation of secretion is maintained over a longer period. The data demonstrate fundamental differences between LDCV dynamics in axons and growth cones under basal conditions. Conclusions Under basal conditions, LDCVs move faster away from the soma than toward the soma, but fewer LDCVs travel anterograde than retrograde. Stimulation decreased average anterograde velocity and increases granule pausing. Data from antibody uptake, quantification of enzyme secretion and appearance of pHluorin fluorescence demonstrate distributed release of peptides all along the axon, not just at terminals.

  1. Two-step relaxation mode analysis with multiple evolution times applied to all-atom molecular dynamics protein simulation

    Science.gov (United States)

    Karasawa, N.; Mitsutake, A.; Takano, H.

    2017-12-01

    Proteins implement their functionalities when folded into specific three-dimensional structures, and their functions are related to the protein structures and dynamics. Previously, we applied a relaxation mode analysis (RMA) method to protein systems; this method approximately estimates the slow relaxation modes and times via simulation and enables investigation of the dynamic properties underlying the protein structural fluctuations. Recently, two-step RMA with multiple evolution times has been proposed and applied to a slightly complex homopolymer system, i.e., a single [n ] polycatenane. This method can be applied to more complex heteropolymer systems, i.e., protein systems, to estimate the relaxation modes and times more accurately. In two-step RMA, we first perform RMA and obtain rough estimates of the relaxation modes and times. Then, we apply RMA with multiple evolution times to a small number of the slowest relaxation modes obtained in the previous calculation. Herein, we apply this method to the results of principal component analysis (PCA). First, PCA is applied to a 2-μ s molecular dynamics simulation of hen egg-white lysozyme in aqueous solution. Then, the two-step RMA method with multiple evolution times is applied to the obtained principal components. The slow relaxation modes and corresponding relaxation times for the principal components are much improved by the second RMA.

  2. NF-κB (p65) negatively regulates myocardin-induced cardiomyocyte hypertrophy through multiple mechanisms.

    Science.gov (United States)

    Liao, Xing-Hua; Wang, Nan; Zhao, Dong-Wei; Zheng, De-Liang; Zheng, Li; Xing, Wen-Jing; Zhou, Hao; Cao, Dong-Sun; Zhang, Tong-Cun

    2014-12-01

    Myocardin is well known to play a key role in the development of cardiomyocyte hypertrophy. But the exact molecular mechanism regulating myocardin stability and transactivity to affect cardiomyocyte hypertrophy has not been studied clearly. We now report that NF-κB (p65) can inhibit myocardin-induced cardiomyocyte hypertrophy. Then we explore the molecular mechanism of this response. First, we show that p65 can functionally repress myocardin transcriptional activity and also reduce the protein expression of myocardin. Second, the function of myocardin can be regulated by epigenetic modifications. Myocardin sumoylation is known to transactivate cardiac genes, but whether p65 can inhibit SUMO modification of myocardin is still not clear. Our data show that p65 weakens myocardin transcriptional activity through attenuating SUMO modification of myocardin by SUMO1/PIAS1, thereby impairing myocardin-mediated cardiomyocyte hypertrophy. Furthermore, the expression of myocardin can be regulated by several microRNAs, which play important roles in the development and function of the heart and muscle. We next investigated potential role of miR-1 in cardiac hypotrophy. Our results show that p65 can upregulate the level of miR-1 and miR-1 can decrease protein expression of myocardin in cardiac myocytes. Notably, miR-1 expression is also controlled by myocardin, leading to a feedback loop. These data thus provide important and novel insights into the function that p65 inhibits myocardin-mediated cardiomyocyte hypertrophy by downregulating the expression and SUMO modification of myocardin and enhancing the expression of miR-1. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. The Notch Ligand Delta-Like 4 Regulates Multiple Stages of Early Hemato-Vascular Development

    Science.gov (United States)

    Neves, Hélia; Gomes, Andreia C.; Saavedra, Pedro; Carvalho, Catarina C.; Duarte, António; Cidadão, António; Parreira, Leonor

    2012-01-01

    Background In mouse embryos, homozygous or heterozygous deletions of the gene encoding the Notch ligand Dll4 result in early embryonic death due to major defects in endothelial remodeling in the yolk sac and embryo. Considering the close developmental relationship between endothelial and hematopoietic cell lineages, which share a common mesoderm-derived precursor, the hemangioblast, and many key regulatory molecules, we investigated whether Dll4 is also involved in the regulation of early embryonic hematopoiesis. Methodology/Principal Findings Using Embryoid Bodies (EBs) derived from embryonic stem cells harboring hetero- or homozygous Dll4 deletions, we observed that EBs from both genotypes exhibit an abnormal endothelial remodeling in the vascular sprouts that arise late during EB differentiation, indicating that this in vitro system recapitulates the angiogenic phenotype of Dll4 mutant embryos. However, analysis of EB development at early time points revealed that the absence of Dll4 delays the emergence of mesoderm and severely reduces the number of blast-colony forming cells (BL-CFCs), the in vitro counterpart of the hemangioblast, and of endothelial cells. Analysis of colony forming units (CFU) in EBs and yolk sacs from Dll4+/− and Dll4−/− embryos, showed that primitive erythropoiesis is specifically affected by Dll4 insufficiency. In Dll4 mutant EBs, smooth muscle cells (SMCs) were seemingly unaffected and cardiomyocyte differentiation was increased, indicating that SMC specification is Dll4-independent while a normal dose of this Notch ligand is essential for the quantitative regulation of cardiomyogenesis. Conclusions/Significance This study highlights a previously unnoticed role for Dll4 in the quantitative regulation of early hemato-vascular precursors, further indicating that it is also involved on the timely emergence of mesoderm in early embryogenesis. PMID:22514637

  4. Subcellular targeting and dynamic regulation of PTEN: Implications for neuronal cells and neurological disorders

    Directory of Open Access Journals (Sweden)

    Patricia eKreis

    2014-04-01

    Full Text Available PTEN is a lipid and protein phosphatase that regulates a diverse range of cellular mechanisms. PTEN is mainly present in the cytosol and transiently associates with the plasma membrane to dephosphorylate PI(3,4,5P3, thereby antagonizing the PI3-Kinase signaling pathway. Recently, PTEN has been shown to associate also with organelles such as the endoplasmic reticulum, the mitochondria or the nucleus, and to be secreted outside of the cell. In addition, PTEN dynamically localizes to specialized sub-cellular compartments such as the neuronal growth cone or dendritic spines. The diverse localizations of PTEN imply a tight temporal and spatial regulation, orchestrated by mechanisms such as posttranslational modifications, formation of distinct protein-protein interactions or the activation/recruitment of PTEN downstream of external cues. The regulation of PTEN function is thus not only important at the enzymatic activity level, but is also associated to its spatial distribution. In this review we will summarize (i recent findings that highlight mechanisms controlling PTEN movement and sub-cellular localization, and (ii current understanding of how PTEN localization is achieved by mechanisms controlling posttranslational modification, by association with binding partners and by PTEN structural or activity requirements. Finally, we will discuss the possible roles of compartmentalized PTEN in developing and mature neurons in health and disease.

  5. Subcellular targeting and dynamic regulation of PTEN: implications for neuronal cells and neurological disorders

    Science.gov (United States)

    Kreis, Patricia; Leondaritis, George; Lieberam, Ivo; Eickholt, Britta J.

    2014-01-01

    PTEN is a lipid and protein phosphatase that regulates a diverse range of cellular mechanisms. PTEN is mainly present in the cytosol and transiently associates with the plasma membrane to dephosphorylate PI(3,4,5)P3, thereby antagonizing the PI3-Kinase signaling pathway. Recently, PTEN has been shown to associate also with organelles such as the endoplasmic reticulum (ER), the mitochondria, or the nucleus, and to be secreted outside of the cell. In addition, PTEN dynamically localizes to specialized sub-cellular compartments such as the neuronal growth cone or dendritic spines. The diverse localizations of PTEN imply a tight temporal and spatial regulation, orchestrated by mechanisms such as posttranslational modifications, formation of distinct protein–protein interactions, or the activation/recruitment of PTEN downstream of external cues. The regulation of PTEN function is thus not only important at the enzymatic activity level, but is also associated to its spatial distribution. In this review we will summarize (i) recent findings that highlight mechanisms controlling PTEN movement and sub-cellular localization, and (ii) current understanding of how PTEN localization is achieved by mechanisms controlling posttranslational modification, by association with binding partners and by PTEN structural or activity requirements. Finally, we will discuss the possible roles of compartmentalized PTEN in developing and mature neurons in health and disease. PMID:24744697

  6. GlnK Facilitates the Dynamic Regulation of Bacterial Nitrogen Assimilation

    Science.gov (United States)

    Gosztolai, Adam; Schumacher, Jörg; Behrends, Volker; Bundy, Jacob G.; Heydenreich, Franziska; Bennett, Mark H.; Buck, Martin; Barahona, Mauricio

    2017-05-01

    Ammonium assimilation in E. coli is regulated by two paralogous proteins (GlnB and GlnK), which orchestrate interactions with regulators of gene expression, transport proteins and metabolic pathways. Yet how they conjointly modulate the activity of glutamine synthetase (GS), the key enzyme for nitrogen assimilation, is poorly understood. We combine experiments and theory to study the dynamic roles of GlnB and GlnK during nitrogen starvation and upshift. We measure time-resolved in vivo concentrations of metabolites, total and post-translationally modified proteins, and develop a concise biochemical model of GlnB and GlnK that incorporates competition for active and allosteric sites, as well as functional sequestration of GlnK. The model predicts the responses of GS, GlnB and GlnK under time-varying external ammonium level in the wild type and two genetic knock-outs. Our results show that GlnK is tightly regulated under nitrogen-rich conditions, yet it is expressed during ammonium run-out and starvation. This suggests a role for GlnK as a buffer of nitrogen shock after starvation, and provides a further functional link between nitrogen and carbon metabolisms.

  7. Disorders of Transcriptional Regulation: An Emerging Category of Multiple Malformation Syndromes

    Science.gov (United States)

    Izumi, Kosuke

    2016-01-01

    Some genetic disorders caused by mutations in genes encoding components of the transcriptional machinery as well as proteins involved in epigenetic modification of the genome share many overlapping features, such as facial dysmorphisms, growth problems and developmental delay/intellectual disability. As a basis for some shared phenotypic characteristics in these syndromes, a similar transcriptome disturbance, characterized by global transcriptional dysregulation, is believed to play a major role. In this review article, a general overview of gene transcription is provided, and the current knowledge of the mechanisms underlying some disorders of transcriptional regulation, such as Rubinstein- Taybi, Coffin-Siris, Cornelia de Lange, and CHOPS syndromes, are discussed. PMID:27867341

  8. Multiple Signaling Pathways Coordinately Regulate Forgetting of Olfactory Adaptation through Control of Sensory Responses in Caenorhabditis elegans.

    Science.gov (United States)

    Kitazono, Tomohiro; Hara-Kuge, Sayuri; Matsuda, Osamu; Inoue, Akitoshi; Fujiwara, Manabi; Ishihara, Takeshi

    2017-10-18

    invertebrates. We found that in Caenorhabditis elegans hermaphrodite, the noncell autonomous regulations of forgetting of olfactory adaptation is regulated by three conserved proteins: a membrane protein, MACO-1; a receptor tyrosine kinase, SCD-2: and its ligand, HEN-1. MACO-1 and SCD-2/HEN-1, working in coordination, accelerate forgetting by controlling sensory responses in parallel. Furthermore, temporal regulation of neuronal activity is important for proper forgetting. We suggest that multiple pathways may coordinately and temporally regulate forgetting through control of sensory responses. This study should lead to a better understanding of forgetting in higher organisms. Copyright © 2017 the authors 0270-6474/17/3710240-12$15.00/0.

  9. Calibration of measurement sensitivities of multiple micro-cantilever dynamic modes in atomic force microscopy using a contact detection method

    International Nuclear Information System (INIS)

    Liu Zhen; Jeong, Younkoo; Menq, Chia-Hsiang

    2013-01-01

    An accurate experimental method is proposed for on-spot calibration of the measurement sensitivities of multiple micro-cantilever dynamic modes in atomic force microscopy. One of the key techniques devised for this method is a reliable contact detection mechanism that detects the tip-surface contact instantly. At the contact instant, the oscillation amplitude of the tip deflection, converted to that of the deflection signal in laser reading through the measurement sensitivity, exactly equals to the distance between the sample surface and the cantilever base position. Therefore, the proposed method utilizes the recorded oscillation amplitude of the deflection signal and the base position of the cantilever at the contact instant for the measurement sensitivity calibration. Experimental apparatus along with various signal processing and control modules was realized to enable automatic and rapid acquisition of multiple sets of data, with which the calibration of a single dynamic mode could be completed in less than 1 s to suppress the effect of thermal drift and measurement noise. Calibration of the measurement sensitivities of the first and second dynamic modes of three micro-cantilevers having distinct geometries was successfully demonstrated. The dependence of the measurement sensitivity on laser spot location was also experimentally investigated. Finally, an experiment was performed to validate the calibrated measurement sensitivity of the second dynamic mode of a micro-cantilever.

  10. Whole-body MRI, dynamic contrast-enhanced MRI, and diffusion-weighted imaging for the staging of multiple myeloma

    Energy Technology Data Exchange (ETDEWEB)

    Dutoit, Julie C.; Verstraete, Koenraad L. [Ghent University Hospital, Department of Radiology, Ghent (Belgium)

    2017-06-15

    Magnetic resonance imaging (MRI) is the most sensitive imaging technique for the detection of bone marrow infiltration, and has therefore recently been included in the new diagnostic myeloma criteria, as proposed by the International Myeloma Working Group. Nevertheless, conventional MRI only provides anatomical information and is therefore only of limited use in the response assessment of patients with multiple myeloma. The additional information from functional MRI techniques, such as diffusion-weighted imaging and dynamic contrast-enhanced MRI, can improve the detection rate of bone marrow infiltration and the assessment of response. This can further enhance the sensitivity and specificity of MRI in the staging of multiple myeloma patients. This article provides an overview of the technical aspects of conventional and functional MRI techniques with practical recommendations. It reviews the diagnostic performance, prognostic value, and role in therapy assessment in multiple myeloma and its precursor stages. (orig.)

  11. CHIP regulates bone mass by targeting multiple TRAF family members in bone marrow stromal cells.

    Science.gov (United States)

    Wang, Tingyu; Li, Shan; Yi, Dan; Zhou, Guang-Qian; Chang, Zhijie; Ma, Peter X; Xiao, Guozhi; Chen, Di

    2018-01-01

    Carboxyl terminus of Hsp70-interacting protein (CHIP or STUB1) is an E3 ligase and regulates the stability of several proteins which are involved in different cellular functions. Our previous studies demonstrated that Chip deficient mice display bone loss phenotype due to increased osteoclast formation through enhancing TRAF6 activity in osteoclasts. In this study we provide novel evidence about the function of CHIP. We found that osteoblast differentiation and bone formation were also decreased in Chip KO mice. In bone marrow stromal (BMS) cells derived from Chip -/- mice, expression of a panel of osteoblast marker genes was significantly decreased. ALP activity and mineralized bone matrix formation were also reduced in Chip- deficient BMS cells. We also found that in addition to the regulation of TRAF6, CHIP also inhibits TNFα-induced NF-κB signaling through promoting TRAF2 and TRAF5 degradation. Specific deletion of Chip in BMS cells downregulated expression of osteoblast marker genes which could be reversed by the addition of NF-κB inhibitor. These results demonstrate that the osteopenic phenotype observed in Chip -/- mice was due to the combination of increased osteoclast formation and decreased osteoblast differentiation. Taken together, our findings indicate a significant role of CHIP in bone remodeling.

  12. Multiple miRNAs jointly regulate the biosynthesis of ecdysteroid in the holometabolous insects, Chilo suppressalis.

    Science.gov (United States)

    He, Kang; Sun, Yang; Xiao, Huamei; Ge, Chang; Li, Fei; Han, Zhaojun

    2017-12-01

    The accurate rise and fall of active hormones is important for insect development. The ecdysteroids must be cleared in a timely manner. However, the mechanism of suppressing the ecdysteroid biosynthesis at the right time remains unclear. Here, we sequenced a small RNA library of Chilo suppressalis and identified 300 miRNAs in this notorious rice insect pest. Microarray analysis yielded 54 differentially expressed miRNAs during metamorphosis development. Target prediction and in vitro dual-luciferase assays confirmed that seven miRNAs (two conserved and five novel miRNAs) jointly targeted three Halloween genes in the ecdysteroid biosynthesis pathway. Overexpression of these seven miRNAs reduced the titer of 20-hydroxyecdysone (20E), induced mortality, and retarded development, which could be rescued by treatment with 20E. Comparative analysis indicated that the miRNA regulation of metamorphosis development is a conserved process but that the miRNAs involved are highly divergent. In all, we present evidence that both conserved and lineage-specific miRNAs have crucial roles in regulating development in insects by controlling ecdysteroid biosynthesis, which is important for ensuring developmental convergence and evolutionary diversity. © 2017 He et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  13. A Hox Gene, Antennapedia, Regulates Expression of Multiple Major Silk Protein Genes in the Silkworm Bombyx mori*

    Science.gov (United States)

    Tsubota, Takuya; Tomita, Shuichiro; Uchino, Keiro; Kimoto, Mai; Takiya, Shigeharu; Kajiwara, Hideyuki; Yamazaki, Toshimasa; Sezutsu, Hideki

    2016-01-01

    Hox genes play a pivotal role in the determination of anteroposterior axis specificity during bilaterian animal development. They do so by acting as a master control and regulating the expression of genes important for development. Recently, however, we showed that Hox genes can also function in terminally differentiated tissue of the lepidopteran Bombyx mori. In this species, Antennapedia (Antp) regulates expression of sericin-1, a major silk protein gene, in the silk gland. Here, we investigated whether Antp can regulate expression of multiple genes in this tissue. By means of proteomic, RT-PCR, and in situ hybridization analyses, we demonstrate that misexpression of Antp in the posterior silk gland induced ectopic expression of major silk protein genes such as sericin-3, fhxh4, and fhxh5. These genes are normally expressed specifically in the middle silk gland as is Antp. Therefore, the evidence strongly suggests that Antp activates these silk protein genes in the middle silk gland. The putative sericin-1 activator complex (middle silk gland-intermolt-specific complex) can bind to the upstream regions of these genes, suggesting that Antp directly activates their expression. We also found that the pattern of gene expression was well conserved between B. mori and the wild species Bombyx mandarina, indicating that the gene regulation mechanism identified here is an evolutionarily conserved mechanism and not an artifact of the domestication of B. mori. We suggest that Hox genes have a role as a master control in terminally differentiated tissues, possibly acting as a primary regulator for a range of physiological processes. PMID:26814126

  14. Robust Generation of Dynamic Data Structure Visualizations with Multiple Interaction Approaches

    Science.gov (United States)

    Cross, James H., II; Hendrix, T. Dean; Umphress, David A.; Barowski, Larry A.; Jain, Jhilmil; Montgomery, Lacey N.

    2009-01-01

    jGRASP has three integrated approaches for interacting with its dynamic viewers for data structures: debugger, workbench, and text-based interactions that allow individual Java statements and expressions to be executed/evaluated. These approaches can be used together to provide a complementary set of interactions with the dynamic viewers. Data…

  15. Spatial heterogeneity regulates plant-pollinator networks across multiple landscape scales.

    Directory of Open Access Journals (Sweden)

    Eduardo Freitas Moreira

    Full Text Available Mutualistic plant-pollinator interactions play a key role in biodiversity conservation and ecosystem functioning. In a community, the combination of these interactions can generate emergent properties, e.g., robustness and resilience to disturbances such as fluctuations in populations and extinctions. Given that these systems are hierarchical and complex, environmental changes must have multiple levels of influence. In addition, changes in habitat quality and in the landscape structure are important threats to plants, pollinators and their interactions. However, despite the importance of these phenomena for the understanding of biological systems, as well as for conservation and management strategies, few studies have empirically evaluated these effects at the network level. Therefore, the objective of this study was to investigate the influence of local conditions and landscape structure at multiple scales on the characteristics of plant-pollinator networks. This study was conducted in agri-natural lands in Chapada Diamantina, Bahia, Brazil. Pollinators were collected in 27 sampling units distributed orthogonally along a gradient of proportion of agriculture and landscape diversity. The Akaike information criterion was used to select models that best fit the metrics for network characteristics, comparing four hypotheses represented by a set of a priori candidate models with specific combinations of the proportion of agriculture, the average shape of the landscape elements, the diversity of the landscape and the structure of local vegetation. The results indicate that a reduction of habitat quality and landscape heterogeneity can cause species loss and decrease of networks nestedness. These structural changes can reduce robustness and resilience of plant-pollinator networks what compromises the reproductive success of plants, the maintenance of biodiversity and the pollination service stability. We also discuss the possible explanations for

  16. Spatial heterogeneity regulates plant-pollinator networks across multiple landscape scales.

    Science.gov (United States)

    Moreira, Eduardo Freitas; Boscolo, Danilo; Viana, Blandina Felipe

    2015-01-01

    Mutualistic plant-pollinator interactions play a key role in biodiversity conservation and ecosystem functioning. In a community, the combination of these interactions can generate emergent properties, e.g., robustness and resilience to disturbances such as fluctuations in populations and extinctions. Given that these systems are hierarchical and complex, environmental changes must have multiple levels of influence. In addition, changes in habitat quality and in the landscape structure are important threats to plants, pollinators and their interactions. However, despite the importance of these phenomena for the understanding of biological systems, as well as for conservation and management strategies, few studies have empirically evaluated these effects at the network level. Therefore, the objective of this study was to investigate the influence of local conditions and landscape structure at multiple scales on the characteristics of plant-pollinator networks. This study was conducted in agri-natural lands in Chapada Diamantina, Bahia, Brazil. Pollinators were collected in 27 sampling units distributed orthogonally along a gradient of proportion of agriculture and landscape diversity. The Akaike information criterion was used to select models that best fit the metrics for network characteristics, comparing four hypotheses represented by a set of a priori candidate models with specific combinations of the proportion of agriculture, the average shape of the landscape elements, the diversity of the landscape and the structure of local vegetation. The results indicate that a reduction of habitat quality and landscape heterogeneity can cause species loss and decrease of networks nestedness. These structural changes can reduce robustness and resilience of plant-pollinator networks what compromises the reproductive success of plants, the maintenance of biodiversity and the pollination service stability. We also discuss the possible explanations for these relationships and

  17. Spatial Heterogeneity Regulates Plant-Pollinator Networks across Multiple Landscape Scales

    Science.gov (United States)

    Moreira, Eduardo Freitas; Boscolo, Danilo; Viana, Blandina Felipe

    2015-01-01

    Mutualistic plant-pollinator interactions play a key role in biodiversity conservation and ecosystem functioning. In a community, the combination of these interactions can generate emergent properties, e.g., robustness and resilience to disturbances such as fluctuations in populations and extinctions. Given that these systems are hierarchical and complex, environmental changes must have multiple levels of influence. In addition, changes in habitat quality and in the landscape structure are important threats to plants, pollinators and their interactions. However, despite the importance of these phenomena for the understanding of biological systems, as well as for conservation and management strategies, few studies have empirically evaluated these effects at the network level. Therefore, the objective of this study was to investigate the influence of local conditions and landscape structure at multiple scales on the characteristics of plant-pollinator networks. This study was conducted in agri-natural lands in Chapada Diamantina, Bahia, Brazil. Pollinators were collected in 27 sampling units distributed orthogonally along a gradient of proportion of agriculture and landscape diversity. The Akaike information criterion was used to select models that best fit the metrics for network characteristics, comparing four hypotheses represented by a set of a priori candidate models with specific combinations of the proportion of agriculture, the average shape of the landscape elements, the diversity of the landscape and the structure of local vegetation. The results indicate that a reduction of habitat quality and landscape heterogeneity can cause species loss and decrease of networks nestedness. These structural changes can reduce robustness and resilience of plant-pollinator networks what compromises the reproductive success of plants, the maintenance of biodiversity and the pollination service stability. We also discuss the possible explanations for these relationships and

  18. [HSP90 Inhibitor 17-AAG Inhibits Multiple Myeloma Cell Proliferation by Down-regulating Wnt/β-Catenin Signaling Pathway].

    Science.gov (United States)

    Chen, Kan-Kan; He, Zheng-Mei; Ding, Bang-He; Chen, Yue; Zhang, Li-Juan; Yu, Liang; Gao, Jian

    2016-02-01

    To investigate the inhibitory effect of HSP90 inhibitory 17-AAG on proliferation of multiple myeloma cells and its main mechanism. The multiple myeloma cells U266 were treated with 17-AAG of different concentrations (200, 400, 600 and 800 nmol/L) for 24, 48, and 72 hours respectively, then the proliferation rate, expression levels of β-catenin and C-MYC protein, as well as cell cycle of U266 cells were treated with 17-AAG and were detected by MTT method, Western blot and flow cytometry, respectively. The 17-AAG showed inhibitory effect on the proliferation of U266 cells in dose- and time-depetent manners (r = -0.518, P AAG displayed no inhibitory effect on proliferation of U266 cells (P > 0.05). The result of culturing U266 cells for 72 hours by 17-AAG of different concentrations showed that the more high of 17-AAG concentration, the more low level of β-catenin and C-MYC proteins (P AAG concentration, the more high of cell ratio in G1 phase (P AAG, the more long time of culture, the more high of cell ratio in G1 phase (P AAG can inhibit the proliferation of multiple myeloma cells, the down-regulation of Wnt/β-catenin signaling pathway and inhibition of HSP90 expression may be the main mechnisms of 17-AAG effect.

  19. The multiple functions of the endocannabinoid system: a focus on the regulation of food intake

    Directory of Open Access Journals (Sweden)

    Tibiriça Eduardo

    2010-01-01

    Full Text Available Abstract Background Cannabis sativa (also known as marijuana has been cultivated by man for more than 5,000 years. However, there was a rise in its use in the 20th century for recreational, religious or spiritual, and medicinal purposes. The main psychoactive constituent of cannabis, whose structure was identified in the 1960's, is Δ9-tetrahydrocannabinol. On the other hand, the discovery of cannabinoid receptors and their endogenous agonists took place only very recently. In fact, the first cannabinoid receptor (CB1 was cloned in 1990, followed 3 years later by the characterization of a second cannabinoid receptor (CB2. Since the 19th century, the use of cannabis has been reported to stimulate appetite and increase the consumption of sweet and tasty food, sometimes resulting in significant weight gain. The recent description of the endocannabinoid system, not only in the central nervous system but also in peripheral tissues, points to its involvement in the regulation of appetite, food intake and energy metabolism. Consequently, the pharmacological modulation of the over-activity of this system could be useful in the treatment of the metabolic syndrome. Conclusions The endocannabinoid system has important physiological functions not only in the central nervous system but also in peripheral tissues. The activation of central CB1 receptors, particularly in hypothalamic nuclei and in the limbic system, is involved in the regulation of feeding behavior, and especially in the control of the intake of palatable food. In the periphery, cannabinoid receptors are present in adipocytes, skeletal muscle, gastrointestinal tract and liver, modulating energy metabolism.

  20. Non-Suicidal Self-Injury, Sexuality Concerns, and Emotion Regulation among Sexually Diverse Adolescents: A Multiple Mediation Analysis.

    Science.gov (United States)

    Fraser, Gloria; Wilson, Marc Stewart; Garisch, Jessica Anne; Robinson, Kealagh; Brocklesby, Madeleine; Kingi, Tahlia; O'Connell, Angelique; Russell, Lynne

    2017-07-31

    Despite increasing interest in the prevalence and correlates of Non-Suicidal Self-Injury (NSSI) in adolescent populations, relatively few studies have examined NSSI among lesbian, gay and bisexual (LGB) adolescents. The current study explored sexuality concerns and elevated emotion dysregulation as potential mechanisms underlying the relationship between sexual orientation and elevated non-suicidal self-injury (NSSI). A community sample of 1,799 adolescents completed a questionnaire assessing NSSI, sexual orientation, sexuality concerns, and emotion regulation. Across the study, 20.6% of adolescents reported a history of NSSI. Adolescents who identify as "mostly heterosexual," "bisexual," and "mostly homosexual" were more likely to engage in NSSI than gay/lesbian, heterosexual, and asexual adolescents. Multiple mediation analysis showed that emotion regulation, but not sexuality concerns, mediated the relationship between sexual orientation and NSSI. The current study tested two theoretical pathways by which sexual orientation could predict NSSI engagement. Findings suggest that literature on general psychological processes, as well as group-specific minority stressors, can shed light on high rates of NSSI among LGB populations. Specifically, the challenges faced by LGB adolescents may undermine the development of emotion regulation. As such, this should be a key target of intervention with LGB adolescents engaging in NSSI.

  1. INFORMATION MINING OF SPATIO-TEMPORAL EVOLUTION OF LAKES BASED ON MULTIPLE DYNAMIC MEASUREMENTS

    Directory of Open Access Journals (Sweden)

    W. Feng

    2017-09-01

    Full Text Available Lakes are important water resources and integral parts of the natural ecosystem, and it is of great significance to study the evolution of lakes. The area of each lake increased and decreased at the same time in natural condition, only but the net change of lakes’ area is the result of the bidirectional evolution of lakes. In this paper, considering the effects of net fragmentation, net attenuation, swap change and spatial invariant part in lake evolution, a comprehensive evaluation indexes of lake dynamic evolution were defined,. Such degree contains three levels of measurement: 1 the swap dynamic degree (SDD reflects the space activity of lakes in the study period. 2 the attenuation dynamic degree (ADD reflects the net attenuation of lakes into non-lake areas. 3 the fragmentation dynamic degree (FDD reflects the trend of lakes to be divided and broken into smaller lakes. Three levels of dynamic measurement constitute the three-dimensional "Swap - attenuation – fragmentation" dynamic evolution measurement system of lakes. To show its effectiveness, the dynamic measurement was applied to lakes in Jianghan Plain, the middle Yangtze region of China for a more detailed analysis of lakes from 1984 to 2014. In combination with spatial-temporal location characteristics of lakes, the hidden information in lake evolution in the past 30 years can be revealed.

  2. Multiple complexes of nitrogen assimilatory enzymes in spinach chloroplasts: possible mechanisms for the regulation of enzyme function.

    Directory of Open Access Journals (Sweden)

    Yoko Kimata-Ariga

    Full Text Available Assimilation of nitrogen is an essential biological process for plant growth and productivity. Here we show that three chloroplast enzymes involved in nitrogen assimilation, glutamate synthase (GOGAT, nitrite reductase (NiR and glutamine synthetase (GS, separately assemble into distinct protein complexes in spinach chloroplasts, as analyzed by western blots under blue native electrophoresis (BN-PAGE. GOGAT and NiR were present not only as monomers, but also as novel complexes with a discrete size (730 kDa and multiple sizes (>120 kDa, respectively, in the stromal fraction of chloroplasts. These complexes showed the same mobility as each monomer on two-dimensional (2D SDS-PAGE after BN-PAGE. The 730 kDa complex containing GOGAT dissociated into monomers, and multiple complexes of NiR reversibly converted into monomers, in response to the changes in the pH of the stromal solvent. On the other hand, the bands detected by anti-GS antibody were present not only in stroma as a conventional decameric holoenzyme complex of 420 kDa, but also in thylakoids as a novel complex of 560 kDa. The polypeptide in the 560 kDa complex showed slower mobility than that of the 420 kDa complex on the 2D SDS-PAGE, implying the assembly of distinct GS isoforms or a post-translational modification of the same GS protein. The function of these multiple complexes was evaluated by in-gel GS activity under native conditions and by the binding ability of NiR and GOGAT with their physiological electron donor, ferredoxin. The results indicate that these multiplicities in size and localization of the three nitrogen assimilatory enzymes may be involved in the physiological regulation of their enzyme function, in a similar way as recently described cases of carbon assimilatory enzymes.

  3. Recent research and applications of numerical simulation for dynamic response of long-span bridges subjected to multiple loads.

    Science.gov (United States)

    Chen, Zhiwei; Chen, Bo

    2014-01-01

    Many long-span bridges have been built throughout the world in recent years but they are often subject to multiple types of dynamic loads, especially those located in wind-prone regions and carrying both trains and road vehicles. To ensure the safety and functionality of these bridges, dynamic responses of long-span bridges are often required for bridge assessment. Given that there are several limitations for the assessment based on field measurement of dynamic responses, a promising approach is based on numerical simulation technologies. This paper provides a detailed review of key issues involved in dynamic response analysis of long-span multiload bridges based on numerical simulation technologies, including dynamic interactions between running trains and bridge, between running road vehicles and bridge, and between wind and bridge, and in the wind-vehicle-bridge coupled system. Then a comprehensive review is conducted for engineering applications of newly developed numerical simulation technologies to safety assessment of long-span bridges, such as assessment of fatigue damage and assessment under extreme events. Finally, the existing problems and promising research efforts for the numerical simulation technologies and their applications to assessment of long-span multiload bridges are explored.

  4. The Legionella pneumophila Dps homolog is regulated by iron and involved in multiple stress tolerance.

    Science.gov (United States)

    Yu, Ming-Jia; Ren, Jun; Zeng, Yong-Lun; Zhou, Shi-Ning; Lu, Yong-Jun

    2009-09-01

    Iron homeostasis is essential to almost all organisms. In this study, we identified the putative homolog of the iron-storage protein-encoding gene, dpsL, in the intracellular pathogen Legionella pneumophila and demonstrated its expression under iron-limited conditions and its responses to multiple stresses. Quantitative real-time PCR analysis indicated that the expression of dpsL was enhanced under iron limitation regardless of the growth phase. Compared with the wild-type cells, the cells devoid of dpsL were heat and H(2)O(2)-sensitive. In contrast to the dps mutants of other bacteria, the growth of the dpsL mutant in an iron-deprived medium was delayed but finally reached the same cell density as wild-type cells during the stationary phase of growth. The finding that the dpsL mutant is salt resistant suggested the involvement of DpsL in virulence. Copyright 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Regulation of an Autoimmune Model for Multiple Sclerosis in Th2-Biased GATA3 Transgenic Mice

    Directory of Open Access Journals (Sweden)

    Viromi Fernando

    2014-01-01

    Full Text Available T helper (Th2 cells have been proposed to play a neuroprotective role in multiple sclerosis (MS. This is mainly based on “loss-of-function” studies in an animal model for MS, experimental autoimmune encephalomyelitis (EAE, using blocking antibodies against Th2 related cytokines, and knockout mice lacking Th2-related molecules. We tested whether an increase of Th2 responses (“gain-of-function” approach could alter EAE, the approach of novel GATA binding protein 3 (GATA3-transgenic (tg mice that overexpress GATA3, a transcription factor required for Th2 differentiation. In EAE induced with myelin oligodendrocyte glycoprotein (MOG35−55 peptide, GATA3-tg mice had a significantly delayed onset of disease and a less severe maximum clinical score, compared with wild-type C57BL/6 mice. Histologically, GATA3-tg mice had decreased levels of meningitis and demyelination in the spinal cord, and anti-inflammatory cytokine profiles immunologically, however both groups developed similar levels of MOG-specific lymphoproliferative responses. During the early stage, we detected higher levels of interleukin (IL-4 and IL-10, with MOG and mitogen stimulation of regional lymph node cells in GATA3-tg mice. During the late stage, only mitogen stimulation induced higher IL-4 and lower interferon-γ and IL-17 production in GATA3-tg mice. These results suggest that a preexisting bias toward a Th2 immune response may reduce the severity of inflammatory demyelinating diseases, including MS.

  6. Quorum Sensing Controls Adaptive Immunity through the Regulation of Multiple CRISPR-Cas Systems.

    Science.gov (United States)

    Patterson, Adrian G; Jackson, Simon A; Taylor, Corinda; Evans, Gary B; Salmond, George P C; Przybilski, Rita; Staals, Raymond H J; Fineran, Peter C

    2016-12-15

    Bacteria commonly exist in high cell density populations, making them prone to viral predation and horizontal gene transfer (HGT) through transformation and conjugation. To combat these invaders, bacteria possess an arsenal of defenses, such as CRISPR-Cas adaptive immunity. Many bacterial populations coordinate their behavior as cell density increases, using quorum sensing (QS) signaling. In this study, we demonstrate that QS regulation results in increased expression of the type I-E, I-F, and III-A CRISPR-Cas systems in Serratia cells in high-density populations. Strains unable to communicate via QS were less effective at defending against invaders targeted by any of the three CRISPR-Cas systems. Additionally, the acquisition of immunity by the type I-E and I-F systems was impaired in the absence of QS signaling. We propose that bacteria can use chemical communication to modulate the balance between community-level defense requirements in high cell density populations and host fitness costs of basal CRISPR-Cas activity. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  7. Novel energy-saving strategies to multiple stressors in birds: the ultradian regulation of body temperature.

    Science.gov (United States)

    Tattersall, Glenn J; Roussel, Damien; Voituron, Yann; Teulier, Loïc

    2016-09-28

    This study aimed to examine thermoregulatory responses in birds facing two commonly experienced stressors, cold and fasting. Logging devices allowing long-term and precise access to internal body temperature were placed within the gizzards of ducklings acclimated to cold (CA) (5°C) or thermoneutrality (TN) (25°C). The animals were then examined under three equal 4-day periods: ad libitum feeding, fasting and re-feeding. Through the analysis of daily as well as short-term, or ultradian, variations of body temperature, we showed that while ducklings at TN show only a modest decline in daily thermoregulatory parameters when fasted, they exhibit reduced surface temperatures from key sites of vascular heat exchange during fasting. The CA birds, on the other hand, significantly reduced their short-term variations of body temperature while increasing long-term variability when fasting. This phenomenon would allow the CA birds to reduce the energetic cost of body temperature maintenance under fasting. By analysing ultradian regulation of body temperature, we describe a means by which an endotherm appears to lower thermoregulatory costs in response to the combined stressors of cold and fasting. © 2016 The Author(s).

  8. Multiple functions of DDX3 RNA helicase in gene regulation, tumorigenesis and viral infection

    Directory of Open Access Journals (Sweden)

    YASUO eARIUMI

    2014-12-01

    Full Text Available The DEAD-box RNA helicase DDX3 is a multifunctional protein involved in all aspects of RNA metabolism, including transcription, splicing, mRNA nuclear export, translation, RNA decay and ribosome biogenesis. In addition, DDX3 is also implicated in cell cycle regulation, apoptosis, Wnt-ß-catenin signaling, tumorigenesis, and viral infection. Notably, recent studies suggest that DDX3 is a component of anti-viral innate immune signaling pathways. Indeed, DDX3 contributes to enhance the induction of anti-viral mediators, interferon regulatory factor (IRF 3 and type I interferon (IFN. However, DDX3 seems to be an important target for several viruses, such as human immunodeficiency virus (HIV-1, hepatitis C virus (HCV, hepatitis B virus (HBV, and poxvirus. DDX3 interacts with HIV-1 Rev or HCV Core protein and modulates its function. At least, DDX3 is required for both HIV-1 and HCV replication. Therefore, DDX3 could be a novel therapeutic target for the development of drug against HIV-1 and HCV.

  9. Dynamic regulation of cerebral blood flow and it's clinical, and laboratory markers in elderly patients with arterial hypertension

    Directory of Open Access Journals (Sweden)

    Tikhonova L.A.

    2011-12-01

    Full Text Available Aim: to estimate the dynamic regulation of cerebral blood flow (CBF and significance of clinical, and laboratory parameters as a possible markers of CBF violations. Material. 179 elderly patients with arterial hypertension were involved in the study. Transcranial Doppler ultrasonography (Philips Envisor HD, USA was used for CBF parameters dynamics during orthostatic hypotension. Results. Main directions of CBF parameters changings (Friedman ANOVA p 0,0091 ... 0,012, coeff. of concordance 0,308 ... 0,691 were detected. Gender differences of CBF parameters, as well as blood pressure level influence upon CBF regulation during orthostatic hypertension were studied. Conclusion. Received data allow us to consider gender, controlled or uncontrolled hypertension, cytomorphological parameters of peripheral blood, diuretics usage as clinical, and laboratory markers of dynamic regulation of CBF in elderly patients with arterial hypertension

  10. Regulation of ER-Golgi Transport Dynamics by GTPases in Budding Yeast

    Directory of Open Access Journals (Sweden)

    Yasuyuki Suda

    2018-01-01

    Full Text Available A large number of proteins are synthesized de novo in the endoplasmic reticulum (ER. They are transported through the Golgi apparatus and then delivered to their proper destinations. The ER and the Golgi play a central role in protein processing and sorting and show dynamic features in their forms. Ras super family small GTPases mediate the protein transport through and between these organelles. The ER-localized GTPase, Sar1, facilitates the formation of COPII transport carriers at the ER exit sites (ERES on the ER for the transport of cargo proteins from the ER to the Golgi. The Golgi-localized GTPase, Arf1, controls intra-Golgi, and Golgi-to-ER transport of cargo proteins by the formation of COPI carriers. Rab GTPases localized at the Golgi, which are responsible for fusion of membranes, are thought to establish the identities of compartments. Recent evidence suggests that these small GTPases regulate not only discrete sites for generation/fusion of transport carriers, but also membrane dynamics of the organelles where they locate to ensure the integrity of transport. Here we summarize the current understandings about the membrane traffic between these organelles and highlight the cutting-edge advances from super-resolution live imaging of budding yeast, Saccharomyces cerevisiae.

  11. Phosphorylation of SNAP-23 regulates its dynamic membrane association during mast cell exocytosis

    Directory of Open Access Journals (Sweden)

    Pieu Naskar

    2017-09-01

    Full Text Available Upon allergen challenge, mast cells (MCs respond by releasing pre-stored mediators from their secretory granules by the transient mechanism of porosome-mediated cell secretion. The target SNARE SNAP-23 has been shown to be important for MC exocytosis, and our previous studies revealed the presence of one basal (Thr102 and two induced (Ser95 and Ser120 phosphorylation sites in its linker region. To study the role of SNAP-23 phosphorylation in the regulation of exocytosis, green fluorescence protein-tagged wild-type SNAP-23 (GFP-SNAP-23 and its phosphorylation mutants were transfected into rat basophilic leukemia (RBL-2H3 MCs. Studies on GFP-SNAP-23 transfected MCs revealed some dynamic changes in SNAP-23 membrane association. SNAP-23 was associated with plasma membrane in resting MCs, however, on activation a portion of it translocated to cytosol and internal membranes. These internal locations were secretory granule membranes. This dynamic change in the membrane association of SNAP-23 in MCs may be important for mediating internal granule-granule fusions in compound exocytosis. Further studies with SNAP-23 phosphorylation mutants revealed an important role for the phosphorylation at Thr102 in its initial membrane association, and of induced phosphorylation at Ser95 and Ser120 in its internal membrane association, during MC exocytosis.

  12. Dynamic pattern of prices under price-cap regulation; Price cap kiseika no ryokin hendo pattern

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, H. [Central Research Institute of Electric Power Industry, Tokyo (Japan)

    1997-07-01

    In this analysis, a power rate determination model was developed for numerical experiment, a dynamic pattern of prices under price-cap regulation (PCR) which has been overlooked in the analysis, and a study was made on if the Ramsey pricing can be realized. A power rate determination simulation model was developed which maximizes a total amount of profits from corporate acts under PCR. By expanding the model in future, policy simulations on PCR under various conditions became possible. With relation to the rate determination act under PCR, two cases were assumed for the simulational comparison: the case in which competition is introduced into the power sector, and the case in which both the power sector and lighting sector are monopolistic for comparison with the former case. As a result, it was confirmed that in any cases the rate of power demand which is relatively price-dynamic under PCR largely declined and contrarily the lighting rate soars. 12 refs., 5 figs., 13 tabs.

  13. CD8+ T-Cells as Immune Regulators of Multiple Sclerosis

    Science.gov (United States)

    Sinha, Sushmita; Boyden, Alexander W.; Itani, Farah R.; Crawford, Michael P.; Karandikar, Nitin J.

    2015-01-01

    The vast majority of studies regarding the immune basis of MS (and its animal model, EAE) have largely focused on CD4+ T-cells as mediators and regulators of disease. Interestingly, CD8+ T-cells represent the predominant T-cell population in human MS lesions and are oligoclonally expanded at the site of pathology. However, their role in the autoimmune pathologic process has been both understudied and controversial. Several animal models and MS patient studies support a pathogenic role for CNS-specific CD8+ T-cells, whereas we and others have demonstrated a regulatory role for these cells in disease. In this review, we describe studies that have investigated the role of CD8+ T-cells in MS and EAE, presenting evidence for both pathogenic and regulatory functions. In our studies, we have shown that cytotoxic/suppressor CD8+ T-cells are CNS antigen-specific, MHC class I-restricted, IFNγ- and perforin-dependent, and are able to inhibit disease. The clinical relevance for CD8+ T-cell suppressive function is best described by a lack of their function during MS relapse, and importantly, restoration of their suppressive function during quiescence. Furthermore, CD8+ T-cells with immunosuppressive functions can be therapeutically induced in MS patients by glatiramer acetate (GA) treatment. Unlike CNS-specific CD8+ T-cells, these immunosuppressive GA-induced CD8+ T-cells appear to be HLA-E restricted. These studies have provided greater fundamental insight into the role of autoreactive as well as therapeutically induced CD8+ T-cells in disease amelioration. The clinical implications for these findings are immense and we propose that this natural process can be harnessed toward the development of an effective immunotherapeutic strategy. PMID:26697014

  14. Impacts of small scale flow regulation on sediment dynamics in an ecologically important upland river.

    Science.gov (United States)

    Quinlan, E; Gibbins, C N; Batalla, R J; Vericat, D

    2015-03-01

    Flow regulation is widely recognized as affecting fluvial processes and river ecosystems. Most impact assessments have focused on large dams and major water transfer schemes, so relatively little is known about the impacts of smaller dams, weirs and water diversions. This paper assesses sediment dynamics in an upland river (the Ehen, NW England) whose flows are regulated by a small weir and tributary diversion. The river is important ecologically due to the presence of the endangered freshwater pearl mussel Margaritifera margaritifera, a species known to be sensitive to sedimentary conditions. Fine sediment yield for the 300-m long study reach was estimated to be 0.057 t km(-2) year(-1), a very low value relative to other upland UK rivers. Mean in-channel storage of fine sediment was also low, estimated at an average of around 40 g m(-2). Although the study period was characterized by frequent high flow events, little movement of coarser bed material was observed. Data therefore indicate an extremely stable fluvial system within the study reach. The implication of this stability for pearl mussels is discussed.

  15. Dynamic intramolecular regulation of the histone chaperone nucleoplasmin controls histone binding and release.

    Science.gov (United States)

    Warren, Christopher; Matsui, Tsutomu; Karp, Jerome M; Onikubo, Takashi; Cahill, Sean; Brenowitz, Michael; Cowburn, David; Girvin, Mark; Shechter, David

    2017-12-20

    Nucleoplasmin (Npm) is a highly conserved histone chaperone responsible for the maternal storage and zygotic release of histones H2A/H2B. Npm contains a pentameric N-terminal core domain and an intrinsically disordered C-terminal tail domain. Though intrinsically disordered regions are common among histone chaperones, their roles in histone binding and chaperoning remain unclear. Using an NMR-based approach, here we demonstrate that the Xenopus laevis Npm tail domain controls the binding of histones at its largest acidic stretch (A2) via direct competition with both the C-terminal basic stretch and basic nuclear localization signal. NMR and small-angle X-ray scattering (SAXS) structural analyses allowed us to construct models of both the tail domain and the pentameric complex. Functional analyses demonstrate that these competitive intramolecular interactions negatively regulate Npm histone chaperone activity in vitro. Together these data establish a potentially generalizable mechanism of histone chaperone regulation via dynamic and specific intramolecular shielding of histone interaction sites.

  16. Ornithine decarboxylase and extracellular polyamines regulate microvascular sprouting and actin cytoskeleton dynamics in endothelial cells

    International Nuclear Information System (INIS)

    Kucharzewska, Paulina; Welch, Johanna E.; Svensson, Katrin J.; Belting, Mattias

    2010-01-01

    The polyamines are essential for cancer cell proliferation during tumorigenesis. Targeted inhibition of ornithine decarboxylase (ODC), i.e. a key enzyme of polyamine biosynthesis, by α-difluoromethylornithine (DFMO) has shown anti-neoplastic activity in various experimental models. This activity has mainly been attributed to the anti-proliferative effect of DFMO in cancer cells. Here, we provide evidence that unperturbed ODC activity is a requirement for proper microvessel sprouting ex vivo as well as the migration of primary human endothelial cells. DFMO-mediated ODC inhibition was reversed by extracellular polyamine supplementation, showing that anti-angiogenic effects of DFMO were specifically related to polyamine levels. ODC inhibition was associated with an abnormal morphology of the actin cytoskeleton during cell spreading and migration. Moreover, our data suggest that de-regulated actin cytoskeleton dynamics in DFMO treated endothelial cells may be related to constitutive activation of the small GTPase CDC42, i.e. a well-known regulator of cell motility and actin cytoskeleton remodeling. These insights into the potential role of polyamines in angiogenesis should stimulate further studies testing the combined anti-tumor effect of polyamine inhibition and established anti-angiogenic therapies in vivo.

  17. A Dynamic Range Expansion Technique for CMOS Image Sensors with Dual Charge Storage in a Pixel and Multiple Sampling

    Directory of Open Access Journals (Sweden)

    Shinya Itoh

    2008-03-01

    Full Text Available A dynamic range expansion technique for CMOS image sensors with dual charge storage in a pixel and multiple sampling technique is presented. Each pixel contains a photodiode and a storage diode which is connected to the photodiode via a separation gate. The sensitivity of the signal charge in the storage diode can be controlled either by a separation gate which limits the charge to flow into the storage diode or by controlling the accumulation time in the storage diode. The operation of the sensitivity control with separation gate techniques is simulated and it is found that a blocking layer to the storage diode plays an important role for high controllability of sensitivity of the storage diode. A prototype chip for testing multiple short time accumulations is fabricated and measured.

  18. A Dynamic Range Expansion Technique for CMOS Image Sensors with Dual Charge Storage in a Pixel and Multiple Sampling

    OpenAIRE

    Shafie, Suhaidi; Kawahito, Shoji; Itoh, Shinya

    2008-01-01

    A dynamic range expansion technique for CMOS image sensors with dual charge storage in a pixel and multiple sampling technique is presented. Each pixel contains a photodiode and a storage diode which is connected to the photodiode via a separation gate. The sensitivity of the signal charge in the storage diode can be controlled either by a separation gate which limits the charge to flow into the storage diode or by controlling the accumulation time in the storage diode. The operation of the s...

  19. Probabilistic assessment of the dynamic interaction between multiple pedestrians and vertical vibrations of footbridges

    Science.gov (United States)

    Tubino, Federica

    2018-03-01

    The effect of human-structure interaction in the vertical direction for footbridges is studied based on a probabilistic approach. The bridge is modeled as a continuous dynamic system, while pedestrians are schematized as moving single-degree-of-freedom systems with random dynamic properties. The non-dimensional form of the equations of motion allows us to obtain results that can be applied in a very wide set of cases. An extensive Monte Carlo simulation campaign is performed, varying the main non-dimensional parameters identified, and the mean values and coefficients of variation of the damping ratio and of the non-dimensional natural frequency of the coupled system are reported. The results obtained can be interpreted from two different points of view. If the characterization of pedestrians' equivalent dynamic parameters is assumed as uncertain, as revealed from a current literature review, then the paper provides a range of possible variations of the coupled system damping ratio and natural frequency as a function of pedestrians' parameters. Assuming that a reliable characterization of pedestrians' dynamic parameters is available (which is not the case at present, but could be in the future), the results presented can be adopted to estimate the damping ratio and natural frequency of the coupled footbridge-pedestrian system for a very wide range of real structures.

  20. Dynamics and waves near multiple magnetic null points in reconnection diffusion region

    Czech Academy of Sciences Publication Activity Database

    Deng, X. H.; Zhou, M.; Li, S. Y.; Baumjohann, W.; Andre, M.; Cornilleau, N.; Santolík, Ondřej; Pontin, D. I.; Reme, H.; Lucek, E.; Fazakerley, A. N.; Decreau, P.; Daly, P.; Nakamura, R.; Tang, R. X.; Hu, Y. H.; Pang, Y.; Büchner, J.; Zhao, H.; Vaivads, A.; Pickett, J. S.; Ng, C. S.; Lin, X.; Fu, S.; Yuan, Z. G.; Su, Z. W.; Wang, J. F.

    2009-01-01

    Roč. 114, - (2009), A07216/1-A07216/7 ISSN 0148-0227 Institutional research plan: CEZ:AV0Z30420517 Keywords : waves * dynamics * reconnection * diffusion Subject RIV: BL - Plasma and Gas Discharge Physics Impact factor: 3.082, year: 2009

  1. Neural Dynamics Associated with Semantic and Episodic Memory for Faces: Evidence from Multiple Frequency Bands

    Science.gov (United States)

    Zion-Golumbic, Elana; Kutas, Marta; Bentin, Shlomo

    2010-01-01

    Prior semantic knowledge facilitates episodic recognition memory for faces. To examine the neural manifestation of the interplay between semantic and episodic memory, we investigated neuroelectric dynamics during the creation (study) and the retrieval (test) of episodic memories for famous and nonfamous faces. Episodic memory effects were evident…

  2. Structural dynamics of surfaces by ultrafast electron crystallography: experimental and multiple scattering theory.

    Science.gov (United States)

    Schäfer, Sascha; Liang, Wenxi; Zewail, Ahmed H

    2011-12-07

    Recent studies in ultrafast electron crystallography (UEC) using a reflection diffraction geometry have enabled the investigation of a wide range of phenomena on the femtosecond and picosecond time scales. In all these studies, the analysis of the diffraction patterns and their temporal change after excitation was performed within the kinematical scattering theory. In this contribution, we address the question, to what extent dynamical scattering effects have to be included in order to obtain quantitative information about structural dynamics. We discuss different scattering regimes and provide diffraction maps that describe all essential features of scatterings and observables. The effects are quantified by dynamical scattering simulations and examined by direct comparison to the results of ultrafast electron diffraction experiments on an in situ prepared Ni(100) surface, for which structural dynamics can be well described by a two-temperature model. We also report calculations for graphite surfaces. The theoretical framework provided here allows for further UEC studies of surfaces especially at larger penetration depths and for those of heavy-atom materials. © 2011 American Institute of Physics

  3. Influence of multiple infection and relatedness on virulence: disease dynamics in an experimental plant population and its castrating parasite.

    Science.gov (United States)

    Buono, Lorenza; López-Villavicencio, Manuela; Shykoff, Jacqui A; Snirc, Alodie; Giraud, Tatiana

    2014-01-01

    The level of parasite virulence, i.e., the decrease in host's fitness due to a pathogen, is expected to depend on several parameters, such as the type of the disease (e.g., castrating or host-killing) and the prevalence of multiple infections. Although these parameters have been extensively studied theoretically, few empirical data are available to validate theoretical predictions. Using the anther smut castrating disease on Silene latifolia caused by Microbotryum lychnidis-dioicae, we studied the dynamics of multiple infections and of different components of virulence (host death, non-recovery and percentage of castrated stems) during the entire lifespan of the host in an experimental population. We monitored the number of fungal genotypes within plants and their relatedness across five years, using microsatellite markers, as well as the rates of recovery and host death in the population. The mean relatedness among genotypes within plants remained at a high level throughout the entire host lifespan despite the dynamics of the disease, with recurrent new infections. Recovery was lower for plants with multiple infections compared to plants infected by a single genotype. As expected for castrating parasites, M. lychnidis-dioicae did not increase host mortality. Mortality varied across years but was generally lower for plants that had been diseased the preceding year. This is one of the few studies to have empirically verified theoretical expectations for castrating parasites, and to show particularly i) that castrated hosts live longer, suggesting that parasites can redirect resources normally used in reproduction to increase host lifespan, lengthening their transmission phase, and ii) that multiple infections increase virulence, here in terms of non-recovery and host castration.

  4. Temporal brain dynamics of multiple object processing: the flexibility of individuation.

    Directory of Open Access Journals (Sweden)

    Veronica Mazza

    Full Text Available The ability to process concurrently multiple visual objects is fundamental for a coherent perception of the world. A core component of this ability is the simultaneous individuation of multiple objects. Many studies have addressed the mechanism of object individuation but it remains unknown whether the visual system mandatorily individuates all relevant elements in the visual field, or whether object indexing depends on task demands. We used a neural measure of visual selection, the N2pc component, to evaluate the flexibility of multiple object individuation. In three ERP experiments, participants saw a variable number of target elements among homogenous distracters and performed either an enumeration task (Experiment 1 or a detection task, reporting whether at least one (Experiment 2 or a specified number of target elements (Experiment 3 was present. While in the enumeration task the N2pc response increased as a function of the number of targets, no such modulation was found in Experiment 2, indicating that individuation of multiple targets is not mandatory. However, a modulation of the N2pc similar to the enumeration task was visible in Experiment 3, further highlighting that object individuation is a flexible mechanism that binds indexes to object properties and locations as needed for further object processing.

  5. Multiplication theory for dynamically biased avalanche photodiodes: new limits for gain bandwidth product.

    Science.gov (United States)

    Hayat, Majeed M; Ramirez, David A

    2012-03-26

    Novel theory is developed for the avalanche multiplication process in avalanche photodiodes (APDs) under time-varying reverse-biasing conditions. Integral equations are derived characterizing the statistics of the multiplication factor and the impulse-response function of APDs, as well as their breakdown probability, all under the assumption that the electric field driving the avalanche process is time varying and spatially nonuniform. Numerical calculations generated by the model predict that by using a bit-synchronous sinusoidal biasing scheme to operate the APD in an optical receiver, the pulse-integrated gain-bandwidth product can be improved by a factor of 5 compared to the same APD operating under the conventional static biasing. The bit-synchronized periodic modulation of the electric field in the multiplication region serves to (1) produce large avalanche multiplication factors with suppressed avalanche durations for photons arriving in the early phase of each optical pulse; and (2) generate low avalanche gains and very short avalanche durations for photons arriving in the latter part of each optical pulse. These two factors can work together to reduce intersymbol interference in optical receivers without sacrificing sensitivity.

  6. Complex Dynamic Scene Perception: Effects of Attentional Set on Perceiving Single and Multiple Event Types

    Science.gov (United States)

    Sanocki, Thomas; Sulman, Noah

    2013-01-01

    Three experiments measured the efficiency of monitoring complex scenes composed of changing objects, or events. All events lasted about 4 s, but in a given block of trials, could be of a single type (single task) or of multiple types (multitask, with a total of four event types). Overall accuracy of detecting target events amid distractors was…

  7. In vitro effect of malachite green on Candida albicans involves multiple pathways and transcriptional regulators UPC2 and STP2.

    Science.gov (United States)

    Dhamgaye, Sanjiveeni; Devaux, Frederic; Manoharlal, Raman; Vandeputte, Patrick; Shah, Abdul Haseeb; Singh, Ashutosh; Blugeon, Corinne; Sanglard, Dominique; Prasad, Rajendra

    2012-01-01

    In this study, we show that a chemical dye, malachite green (MG), which is commonly used in the fish industry as an antifungal, antiparasitic, and antibacterial agent, could effectively kill Candida albicans and non-C. albicans species. We have demonstrated that Candida cells are susceptible to MG at a very low concentration (MIC that reduces growth by 50% [MIC(50)], 100 ng ml(-1)) and that the effect of MG is independent of known antifungal targets, such as ergosterol metabolism and major drug efflux pump proteins. Transcriptional profiling in response to MG treatment of C. albicans cells revealed that of a total of 207 responsive genes, 167 genes involved in oxidative stress, virulence, carbohydrate metabolism, heat shock, amino acid metabolism, etc., were upregulated, while 37 genes involved in iron acquisition, filamentous growth, mitochondrial respiration, etc., were downregulated. We confirmed experimentally that Candida cells exposed to MG resort to a fermentative mode of metabolism, perhaps due to defective respiration. In addition, we showed that MG triggers depletion of intracellular iron pools and enhances reactive oxygen species (ROS) levels. These effects could be reversed by the addition of iron or antioxidants, respectively. We provided evidence that the antifungal effect of MG is exerted through the transcription regulators UPC2 (regulating ergosterol biosynthesis and azole resistance) and STP2 (regulating amino acid permease genes). Taken together, our transcriptome, genetic, and biochemical results allowed us to decipher the multiple mechanisms by which MG exerts its anti-Candida effects, leading to a metabolic shift toward fermentation, increased generation of ROS, labile iron deprivation, and cell necrosis.

  8. Connections Between Future Time Perspectives and Self-Regulated Learning for Mid-Year Engineering Students: A Multiple Case Study

    Science.gov (United States)

    Chasmar, Justine

    This dissertation presents multiple studies with the purpose of understanding the connections between undergraduate engineering students' motivations, specifically students' Future Time Perspectives (FTPs) and Self-Regulated Learning (SRL). FTP refers to the views students hold about the future and how their perceptions of current tasks are affected by these views. SRL connects the behaviors, metacognition, and motivation of students in their learning. The goals of this research project were to 1) qualitatively describe and document engineering students' SRL strategies, 2) examine interactions between engineering students' FTPs and SRL strategy use, and 3) explore goal-setting as a bridge between FTP and SRL. In an exploratory qualitative study with mid-year industrial engineering students to examine the SRL strategies used before and after an SRL intervention, results showed that students intended to use more SRL strategies than they attempted. However, students self-reported using new SRL strategies from the intervention. Students in this population also completed a survey and a single interview about FTP and SRL. Results showed perceptions of instrumentality of coursework and skills as motivation for using SRL strategies, and a varied use of SRL strategies for students with different FTPs. Overall, three types of student FTP were seen: students with a single realistic view of the future, conflicting ideal and realistic future views, or open views of the future. A sequential explanatory mixed methods study was conducted with mid-year students from multiple engineering majors. First a cluster analysis of survey results of FTP items compared to FTP interview responses was used for participant selection. Then a multiple case study was conducted with data collected through surveys, journal entries, course performance, and two interviews. Results showed that students with a well-defined FTP self-regulated in the present based on their varied perceptions of

  9. Autonomous and controlled motivational regulations for multiple health-related behaviors: between- and within-participants analyses.

    Science.gov (United States)

    Hagger, M S; Hardcastle, S J; Chater, A; Mallett, C; Pal, S; Chatzisarantis, N L D

    2014-01-01

    Self-determination theory has been applied to the prediction of a number of health-related behaviors with self-determined or autonomous forms of motivation generally more effective in predicting health behavior than non-self-determined or controlled forms. Research has been confined to examining the motivational predictors in single health behaviors rather than comparing effects across multiple behaviors. The present study addressed this gap in the literature by testing the relative contribution of autonomous and controlling motivation to the prediction of a large number of health-related behaviors, and examining individual differences in self-determined motivation as a moderator of the effects of autonomous and controlling motivation on health behavior. Participants were undergraduate students ( N  = 140) who completed measures of autonomous and controlled motivational regulations and behavioral intention for 20 health-related behaviors at an initial occasion with follow-up behavioral measures taken four weeks later. Path analysis was used to test a process model for each behavior in which motivational regulations predicted behavior mediated by intentions. Some minor idiosyncratic findings aside, between-participants analyses revealed significant effects for autonomous motivational regulations on intentions and behavior across the 20 behaviors. Effects for controlled motivation on intentions and behavior were relatively modest by comparison. Intentions mediated the effect of autonomous motivation on behavior. Within-participants analyses were used to segregate the sample into individuals who based their intentions on autonomous motivation (autonomy-oriented) and controlled motivation (control-oriented). Replicating the between-participants path analyses for the process model in the autonomy- and control-oriented samples did not alter the relative effects of the motivational orientations on intention and behavior. Results provide evidence for consistent effects

  10. Structural and dynamical insights on HLA-DR2 complexes that confer susceptibility to multiple sclerosis in Sardinia: a molecular dynamics simulation study.

    Directory of Open Access Journals (Sweden)

    Amit Kumar

    Full Text Available Sardinia is a major Island in the Mediterranean with a high incidence of multiple sclerosis, a chronic autoimmune inflammatory disease of the central nervous system. Disease susceptibility in Sardinian population has been associated with five alleles of major histocompatibility complex (MHC class II DRB1 gene. We performed 120 ns of molecular dynamics simulation on one predisposing and one protective alleles, unbound and in complex with the two relevant peptides: Myelin Basic Protein and Epstein Barr Virus derived peptide. In particular we focused on the MHC peptide binding groove dynamics. The predisposing allele was found to form a stable complex with both the peptides, while the protective allele displayed stability only when bound with myelin peptide. The local flexibility of the MHC was probed dividing the binding groove into four compartments covering the well known peptide anchoring pockets. The predisposing allele in the first half cleft exhibits a narrower and more rigid groove conformation in the presence of myelin peptide. The protective allele shows a similar behavior, while in the second half cleft it displays a narrower and more flexible groove conformation in the presence of viral peptide. We further characterized these dynamical differences by evaluating H-bonds, hydrophobic and stacking interaction networks, finding striking similarities with super-type patterns emerging in other autoimmune diseases. The protective allele shows a defined preferential binding to myelin peptide, as confirmed by binding free energy calculations. All together, we believe the presented molecular analysis could help to design experimental assays, supports the molecular mimicry hypothesis and suggests that propensity to multiple sclerosis in Sardinia could be partly linked to distinct peptide-MHC interaction and binding characteristics of the antigen presentation mechanism.

  11. Cordycepin Down-Regulates Multiple Drug Resistant (MDR/HIF-1α through Regulating AMPK/mTORC1 Signaling in GBC-SD Gallbladder Cancer Cells

    Directory of Open Access Journals (Sweden)

    Wei-Ding Wu

    2014-07-01

    Full Text Available Gallbladder cancer is the most common malignancy of the bile duct, with low 5-year survival rate and poor prognosis. Novel effective treatments are urgently needed for the therapy of this disease. Here, we showed that cordycepin, the bioactive compound in genus Cordyceps, induced growth inhibition and apoptosis in cultured gallbladder cancer cells (Mz-ChA-1, QBC939 and GBC-SD lines. We found that cordycepin inhibited mTOR complex 1 (mTORC1 activation and down-regulated multiple drug resistant (MDR/hypoxia-inducible factor 1α (HIF-1α expression through activating of AMP-activated protein kinase (AMPK signaling in gallbladder cancer GBC-SD cells. Contrarily, AMPKα1-shRNA depletion dramatically inhibited cordycepin-induced molecular changes as well as GBC-SD cell apoptosis. Further, our results showed that co-treatment with a low concentration cordycepin could remarkably enhance the chemosensitivity of GBC-SD cells to gemcitabine and 5-fluorouracil (5-FU, and the mechanism may be attributed to AMPK activation and MDR degradation. In summary, cordycepin induces growth inhibition and apoptosis in gallbladder cancer cells via activating AMPK signaling. Cordycepin could be a promising new drug or chemo-adjuvant for gallbladder cancer.

  12. The F-actin modifier villin regulates insulin granule dynamics and exocytosis downstream of islet cell autoantigen 512

    Directory of Open Access Journals (Sweden)

    Hassan Mziaut

    2016-08-01

    Conclusion: Our findings show that villin controls the size of the F-actin cages restricting SGs and, thus, regulates their dynamics and availability for exocytosis. Evidence that villin acts downstream of Ica512 also indicates that SGs directly influence the remodeling properties of the cortical actin cytoskeleton for tight control of insulin secretion.

  13. Dynamic Optimization for IPS2 Resource Allocation Based on Improved Fuzzy Multiple Linear Regression

    Directory of Open Access Journals (Sweden)

    Maokuan Zheng

    2017-01-01

    Full Text Available The study mainly focuses on resource allocation optimization for industrial product-service systems (IPS2. The development of IPS2 leads to sustainable economy by introducing cooperative mechanisms apart from commodity transaction. The randomness and fluctuation of service requests from customers lead to the volatility of IPS2 resource utilization ratio. Three basic rules for resource allocation optimization are put forward to improve system operation efficiency and cut unnecessary costs. An approach based on fuzzy multiple linear regression (FMLR is developed, which integrates the strength and concision of multiple linear regression in data fitting and factor analysis and the merit of fuzzy theory in dealing with uncertain or vague problems, which helps reduce those costs caused by unnecessary resource transfer. The iteration mechanism is introduced in the FMLR algorithm to improve forecasting accuracy. A case study of human resource allocation optimization in construction machinery industry is implemented to test and verify the proposed model.

  14. Building the Moon from Multiple Impacts: Merger Efficiency and Dynamical Constraints

    Science.gov (United States)

    Citron, Robert I.; Perets, Hagai B.; Aharonson, Oded

    2017-10-01

    Most aspects of the Earth-Moon system can be explained by the single giant impact hypothesis, but such collisions are rare compared to large impacts that produce smaller satellites. In the multiple-impact hypothesis, the Moon accretes from the mergers of several smaller satellites (moonlets), each formed from debris disks produced by successive impacts Myrs apart, a natural consequence of the Earth's growth through multiple impacts. Using N-body simulations, we assess the likelihood that pre-existing moonlets (which tidally migrate outward) remain stable during subsequent impacts and merge with newly created moonlets. We find that the Earth likely had several previous moons, many of which re-collided with the Earth. We also find that the Moon could have formed from the mergers of several moonlets, which could explain the compositional similarity to the Earth. The stability of moonlets against disruption by subsequent impacts also implies that several large impacts could post-date Moon formation.

  15. KATNAL1 regulation of sertoli cell microtubule dynamics is essential for spermiogenesis and male fertility.

    Directory of Open Access Journals (Sweden)

    Lee B Smith

    Full Text Available Spermatogenesis is a complex process reliant upon interactions between germ cells (GC and supporting somatic cells. Testicular Sertoli cells (SC support GCs during maturation through physical attachment, the provision of nutrients, and protection from immunological attack. This role is facilitated by an active cytoskeleton of parallel microtubule arrays that permit transport of nutrients to GCs, as well as translocation of spermatids through the seminiferous epithelium during maturation. It is well established that chemical perturbation of SC microtubule remodelling leads to premature GC exfoliation demonstrating that microtubule remodelling is an essential component of male fertility, yet the genes responsible for this process remain unknown. Using a random ENU mutagenesis approach, we have identified a novel mouse line displaying male-specific infertility, due to a point mutation in the highly conserved ATPase domain of the novel KATANIN p60-related microtubule severing protein Katanin p60 subunit A-like1 (KATNAL1. We demonstrate that Katnal1 is expressed in testicular Sertoli cells (SC from 15.5 days post-coitum (dpc and that, consistent with chemical disruption models, loss of function of KATNAL1 leads to male-specific infertility through disruption of SC microtubule dynamics and premature exfoliation of spermatids from the seminiferous epithelium. The identification of KATNAL1 as an essential regulator of male fertility provides a significant novel entry point into advancing our understanding of how SC microtubule dynamics promotes male fertility. Such information will have resonance both for future treatment of male fertility and the development of non-hormonal male contraceptives.

  16. Neocortical Dynamics at Multiple Scales: EEG Standing Waves, Statistical Mechanics, and Physical Analogs

    OpenAIRE

    Ingber, Lester; Nunez, Paul L.

    2010-01-01

    The dynamic behavior of scalp potentials (EEG) is apparently due to some combination of global and local processes with important top-down and bottom-up interactions across spatial scales. In treating global mechanisms, we stress the importance of myelinated axon propagation delays and periodic boundary conditions in the cortical-white matter system, which is topologically close to a spherical shell. By contrast, the proposed local mechanisms are multiscale interactions between cortical colum...

  17. Chromogranin A regulates vesicle storage and mitochondrial dynamics to influence insulin secretion.

    Science.gov (United States)

    Wollam, Joshua; Mahata, Sumana; Riopel, Matthew; Hernandez-Carretero, Angelina; Biswas, Angshuman; Bandyopadhyay, Gautam K; Chi, Nai-Wen; Eiden, Lee E; Mahapatra, Nitish R; Corti, Angelo; Webster, Nicholas J G; Mahata, Sushil K

    2017-06-01

    Chromogranin A (CgA) is a prohormone and a granulogenic factor that regulates secretory pathways in neuroendocrine tissues. In β-cells of the endocrine pancreas, CgA is a major cargo in insulin secretory vesicles. The impact of CgA deficiency on the formation and exocytosis of insulin vesicles is yet to be investigated. In addition, no literature exists on the impact of CgA on mitochondrial function in β-cells. Using three different antibodies, we demonstrate that CgA is processed to vasostatin- and catestatin-containing fragments in pancreatic islet cells. CgA deficiency in Chga-KO islets leads to compensatory overexpression of chromogranin B, secretogranin II, SNARE proteins and insulin genes, as well as increased insulin protein content. Ultrastructural studies of pancreatic islets revealed that Chga-KO β-cells contain fewer immature secretory granules than wild-type (WT) control but increased numbers of mature secretory granules and plasma membrane-docked vesicles. Compared to WT control, CgA-deficient β-cells exhibited increases in mitochondrial volume, numerical densities and fusion, as well as increased expression of nuclear encoded genes (Ndufa9, Ndufs8, Cyc1 and Atp5o). These changes in secretory vesicles and the mitochondria likely contribute to the increased glucose-stimulated insulin secretion observed in Chga-KO mice. We conclude that CgA is an important regulator for coordination of mitochondrial dynamics, secretory vesicular quanta and GSIS for optimal secretory functioning of β-cells, suggesting a strong, CgA-dependent positive link between mitochondrial fusion and GSIS.

  18. Response of fish population dynamics to mitigation activities in a large regulated river

    Science.gov (United States)

    Watkins, Carson J.; Ross, Tyler J.; Quist, Michael C.; Hardy, Ryan S.

    2017-01-01

    Extensive water development in large rivers has precipitated many negative ecological effects on native fish populations. Mitigation for such development often focuses on restoring biological integrity through remediation of the physical and chemical properties of regulated rivers. However, evaluating and defining the success of those programs can be difficult. We modeled the influence of mitigation-related environmental factors on growth and recruitment of two ecologically important native fish species (Largescale Sucker Catostomus macrocheilus and Mountain Whitefish Prosopium williamsoni) in the Kootenai River, Idaho. Artificial nutrient (phosphorus) addition best predicted the variability in annual growth of both species. Nutrient addition was positively related to Largescale Sucker growth but negatively related to Mountain Whitefish growth. The best model explained 82% of the annual variability in incremental growth for Largescale Suckers and 61% of the annual variability for Mountain Whitefish. Year-class strength of Largescale Suckers was not closely related to any of the environmental variables evaluated; however, year-class strength of Mountain Whitefish was closely associated with nutrient addition, discharge, and temperature. Most research has focused on biotic assemblages to evaluate the effects of mitigation activities on fishes, but there is an increased need to identify the influence of rehabilitation activities on fish population dynamics within those assemblages. Here, we demonstrate how fish growth can serve as an indicator of rehabilitation success in a highly regulated large river. Future fish restoration projects can likely benefit from a change in scope and from consideration of an evaluation framework involving the response of population rate functions to mitigation.

  19. A dynamic multiple reaction monitoring method for the multiple components quantification of complex traditional Chinese medicine preparations: Niuhuang Shangqing pill as an example.

    Science.gov (United States)

    Liang, Jian; Wu, Wan-ying; Sun, Guo-xiang; Wang, Dan-dan; Hou, Jin-jun; Yang, Wen-zhi; Jiang, Bao-hong; Liu, Xuan; Guo, De-an

    2013-06-14

    It is a challenging task to simultaneously and quantitatively analyze multiple components in DFF [Da-Fu-Fang, namely, complex traditional Chinese medicine (TCM) preparations containing more than ten TCMs] due to their numerous and extreme complex chemical compositions possessing a wide variety of chemical and physical features, and their very low content. Rather than using a conventional mass spectrometry (MS) method with multiple reaction monitoring (MRM), in the current study, this challenge was addressed by using dynamic multiple reaction monitoring (DMRM). Using a DFF, Niuhuang Shangqing pill, which is composed of 19 TCMs, as a model, a rapid (one run in 20min), sensitive [lower limit of detection (LOD) and limit of quantitation (LOQ) were achieved comparable with MRM] and accessible (a standard HPLC/MS/MS instrumentation was employed) MS method was successfully developed for the simultaneous quantification of 41 bioactive components which represented 15 of the 19 medicinal plants. A comparison of LOD and LOQ using MRM and DMRM was made to quantitatively reveal that the latter demonstrated advantages over the former. Meanwhile, a standard operating procedure concerning the development of a new DMRM method was recommended. The MS data were obtained in the positive ion mode with electrospray ionization as the ion source, acetonitrile and water as mobile phase and a Kinetex C18 core-shell column (100mm×2.10mm, 2.6μm, Phenomenex Inc.) as the analytical column. This method was then applied to 32 batches of samples. It transpired, through principal component analysis and orthogonal partial least squares discriminant analysis, that the consistency of the products was relatively good within one company, but poor among different companies among the 32 samples; one failed to qualify in terms of the Chinese Pharmacopeia. This work illustrated that the proposed DMRM method was particularly suitable for quantifying the trace components in DFF and capable of ensuring the

  20. A Dynamic Control Strategy for Hybrid Electric Vehicles Based on Parameter Optimization for Multiple Driving Cycles and Driving Pattern Recognition

    Directory of Open Access Journals (Sweden)

    Zhenzhen Lei

    2017-01-01

    Full Text Available The driving pattern has an important influence on the parameter optimization of the energy management strategy (EMS for hybrid electric vehicles (HEVs. A new algorithm using simulated annealing particle swarm optimization (SA-PSO is proposed for parameter optimization of both the power system and control strategy of HEVs based on multiple driving cycles in order to realize the minimum fuel consumption without impairing the dynamic performance. Furthermore, taking the unknown of the actual driving cycle into consideration, an optimization method of the dynamic EMS based on driving pattern recognition is proposed in this paper. The simulation verifications for the optimized EMS based on multiple driving cycles and driving pattern recognition are carried out using Matlab/Simulink platform. The results show that compared with the original EMS, the former strategy reduces the fuel consumption by 4.36% and the latter one reduces the fuel consumption by 11.68%. A road test on the prototype vehicle is conducted and the effectiveness of the proposed EMS is validated by the test data.

  1. Multiple dynamic Al-based floc layers on ultrafiltration membrane surfaces for humic acid and reservoir water fouling reduction.

    Science.gov (United States)

    Ma, Baiwen; Li, Wenjiang; Liu, Ruiping; Liu, Gang; Sun, Jingqiu; Liu, Huijuan; Qu, Jiuhui; van der Meer, Walter

    2018-04-05

    The integration of adsorbents with ultrafiltration (UF) membranes is a promising method for alleviating membrane fouling and reducing land use. However, adsorbents typically are only injected into the membrane tank once, resulting in a single dynamic protection layer and low removal efficiency over long-term operation. In addition, the granular adsorbents used can cause membrane surface damage. To overcome these disadvantages, we injected inexpensive and loose aluminum (Al)-based flocs directly into a membrane tank with bottom aeration in the presence of humic acid (HA) or raw water taken from the Miyun Reservoir (Beijing, China). Results showed that the flocs were well suspended in the membrane tank, and multiple dynamic floc protection layers were formed (sandwich-like) on the membrane surface with multiple batch injections. Higher frequency floc injections resulted in better floc utilization efficiency and less severe membrane fouling. With continuous injection, acid solutions demonstrated better performance in removing HA molecules, especially those with small molecular weight, and in alleviating membrane fouling compared with the use of high aeration rate or polyacrylamide injection. This was attributed to the small particle size, large specific surface area, and high zeta potential of the flocs. Additionally, excellent UF membrane performance was exhibited by reservoir water with continuous injection and acid solution. Based on the outstanding UF membrane performance, this innovative integrated filtration with loose Al-based flocs has great application potential for water treatment. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. SU-E-T-344: Dynamic Electron Beam Therapy Using Multiple Apertures in a Single Cut-Out

    International Nuclear Information System (INIS)

    Rodrigues, A; Yin, F; Wu, Q

    2015-01-01

    Purpose: Few leaf electron collimators (FLEC) or electron MLCs (eMLC) are highly desirable for dynamic electron beam therapies as they produce multiple apertures within a single delivery to achieve conformal dose distributions. However, their clinical implementation has been challenging. Alternatively, multiple small apertures in a single cut-out with variable jaw sizes could be utilized in a single dynamic delivery. In this study, we investigate dosimetric characteristics of such arrangement. Methods: Monte Carlo (EGSnrc/BEAMnrc/DOSXYnrc) simulations utilized validated Varian TrueBeam phase spaces. Investigated quantities included: Energy (6 MeV), jaw size (1×1 to 22×22 cm 2 ; centered to aperture), applicator/cut-out (15×15 cm 2 ), aperture (1×1, 2×2, 3×3, 4×4 cm 2 ), and aperture placement (on/off central axis). Three configurations were assessed: (1) single aperture on-axis, (2) single aperture off-axis, and (3) multiple apertures. Reference was configuration (1) with standard jaw size. Aperture placement and jaw size were optimized to maintain reference dosimetry and minimize leakage through unused apertures to <5%. Comparison metrics included depth dose and orthogonal profiles. Results: Configuration (1) and (2): Jaw openings were reduced to 10×10 cm 2 without affecting dosimetry (gamma 2%/1mm) regardless of on- or off-axis placement. For smaller jaw sizes, reduced surface (<2%, 5% for 1×1 cm 2 aperture) and increased Bremsstrahlung (<2%, 10% for 1×1 cm 2 aperture) dose was observed. Configuration (3): Optimal aperture placement was in the corners (order: 1×1, 4×4, 2×2, 3×3 cm 2 ) and jaw sizes were 4×4, 4×4, 7×7, and 5×5 cm 2 (apertures: 1×1, 2×2, 3×3, 4×4 cm 2 ). Asymmetric leakage was found from upper and lower jaws. Leakage was generally within 5% with a maximum of 10% observed for the 1×1 cm 2 aperture irradiation. Conclusion: Multiple apertures in a single cut-out with variable jaw size can be used in a single dynamic delivery

  3. Protein kinase A regulates 3-phosphatidylinositide dynamics during platelet-derived growth factor-induced membrane ruffling and chemotaxis.

    Science.gov (United States)

    Deming, Paula B; Campbell, Shirley L; Baldor, Linda C; Howe, Alan K

    2008-12-12

    Spatial regulation of the cAMP-dependent protein kinase (PKA) is required for chemotaxis in fibroblasts; however, the mechanism(s) by which PKA regulates the cell migration machinery remain largely unknown. Here we report that one function of PKA during platelet-derived growth factor (PDGF)-induced chemotaxis was to promote membrane ruffling by regulating phosphatidylinositol 3,4,5-trisphosphate (PIP(3)) dynamics. Inhibition of PKA activity dramatically altered membrane dynamics and attenuated formation of peripheral membrane ruffles in response to PDGF. PKA inhibition also significantly decreased the number and size of PIP(3)-rich membrane ruffles in response to uniform stimulation and to gradients of PDGF. This ruffling defect was quantified using a newly developed method, based on computer vision edge-detection algorithms. PKA inhibition caused a marked attenuation in the bulk accumulation of PIP(3) following PDGF stimulation, without effects on PI3-kinase (PI3K) activity. The deficits in PIP(3) dynamics correlated with a significant inhibition of growth factor-induced membrane recruitment of endogenous Akt and Rac activation in PKA-inhibited cells. Simultaneous inhibition of PKA and Rac had an additive inhibitory effect on growth factor-induced ruffling dynamics. Conversely, the expression of a constitutively active Rac allele was able to rescue the defect in membrane ruffling and restore the localization of a fluorescent PIP(3) marker to membrane ruffles in PKA-inhibited cells, even in the absence of PI3K activity. These data demonstrate that, like Rac, PKA contributes to PIP(3) and membrane dynamics independently of direct regulation of PI3K activity and suggest that modulation of PIP(3)/3-phosphatidylinositol (3-PI) lipids represents a major target for PKA in the regulation of PDGF-induced chemotactic events.

  4. Soil Gas Dynamics and Microbial Activity in the Unsaturated Zone of a Regulated River

    Science.gov (United States)

    Christensen, H.; Ferencz, S. B.; Cardenas, M. B.; Neilson, B. T.; Bennett, P. C.

    2017-12-01

    Over 60% of the world's rivers are dammed, and are therefore regulated. In some river systems, river regulation is the dominant factor governing fluid exchange and soil gas dynamics in the hyporheic region and overlying unsaturated zone of the river banks. Where this is the case, it is important to understand the effects that an artificially-induced change in river stage can have on the chemical, plant, and microbial components of the unsaturated zone. Daily releases from an upstream dam cause rapid stage fluctuations in the Lower Colorado River east of Austin, Texas. For this study, we utilized an array of water and gas wells along a transect perpendicular to the river to investigate the biogeochemical process occurring in this mixing zone. The gas wells were installed at several depths up to 1.5 meters, and facilitated the continuous monitoring of soil gases as the pulse percolated through the river bank. Water samples collected from the screened wells penetrated to depths below the water table and were analyzed for nutrients, carbon, and major ions. Additionally, two soil cores were taken at different distances from the river and analyzed for soil moisture and grain size. These cores were also analyzed for microbial activity using the total heterotroph count method and the acetylene inhibition technique, a sensitive method of measuring denitrifying activity. The results provide a detailed picture of soil gas flux and biogeochemical processes in the bank environment in a regulated river. Findings indicate that a river pulse that causes a meter-scale change in river stage causes small, centimeter-scale pulses in the water table. We propose that these conditions create an area of elevated microbial respiration at the base of the unsaturated zone that appears to be decoupled from normal diurnal fluctuations. Along the transect, CO2 concentrations increased with increasing depth down to the water table. CO2 concentrations were highest in the time following a pulse

  5. Wavelet Imaging on Multiple Scales (WIMS) reveals focal adhesion distributions, dynamics and coupling between actomyosin bundle stability

    Science.gov (United States)

    Toplak, Tim; Palmieri, Benoit; Juanes-García, Alba; Vicente-Manzanares, Miguel; Grant, Martin; Wiseman, Paul W.

    2017-01-01

    We introduce and use Wavelet Imaging on Multiple Scales (WIMS) as an improvement to fluorescence correlation spectroscopy to measure physical processes and features that occur across multiple length scales. In this study, wavelet transforms of cell images are used to characterize molecular dynamics at the cellular and subcellular levels (i.e. focal adhesions). We show the usefulness of the technique by applying WIMS to an image time series of a migrating osteosarcoma cell expressing fluorescently labelled adhesion proteins, which allows us to characterize different components of the cell ranging from optical resolution scale through to focal adhesion and whole cell size scales. Using WIMS we measured focal adhesion numbers, orientation and cell boundary velocities for retraction and protrusion. We also determine the internal dynamics of individual focal adhesions undergoing assembly, disassembly or elongation. Thus confirming as previously shown, WIMS reveals that the number of adhesions and the area of the protruding region of the cell are strongly correlated, establishing a correlation between protrusion size and adhesion dynamics. We also apply this technique to characterize the behavior of adhesions, actin and myosin in Chinese hamster ovary cells expressing a mutant form of myosin IIB (1935D) that displays decreased filament stability and impairs front-back cell polarity. We find separate populations of actin and myosin at each adhesion pole for both the mutant and wild type form. However, we find these populations move rapidly inwards toward one another in the mutant case in contrast to the cells that express wild type myosin IIB where those populations remain stationary. Results obtained with these two systems demonstrate how WIMS has the potential to reveal novel correlations between chosen parameters that belong to different scales. PMID:29049414

  6. Adaptive temperature regulation in the little bird in winter: predictions from a stochastic dynamic programming model.

    Science.gov (United States)

    Brodin, Anders; Nilsson, Jan-Åke; Nord, Andreas

    2017-09-01

    Several species of small birds are resident in boreal forests where environmental temperatures can be -20 to -30 °C, or even lower, in winter. As winter days are short, and food is scarce, winter survival is a challenge for small endothermic animals. A bird of this size will have to gain almost 10% of its lean body mass in fat every day to sustain overnight metabolism. Birds such as parids (titmice and chickadees) can use facultative hypothermia, a process in which body temperature is actively down-regulated to a specific level, to reduce heat loss and thus save energy. During cold winter nights, these birds may decrease body temperature from the normal from 42 ° down to 35 °C, or even lower in some species. However, birds are unable to move in this deep hypothermic state, making it a risky strategy if predators are around. Why, then, do small northern birds enter a potentially dangerous physiological state for a relatively small reduction in energy expenditure? We used stochastic dynamic programming to investigate this. Our model suggests that the use of nocturnal hypothermia at night is paramount in these biomes, as it would increase winter survival for a small northern bird by 58% over a winter of 100 days. Our model also explains the phenomenon known as winter fattening, and its relationship to thermoregulation, in northern birds.

  7. Par6b Regulates the Dynamics of Apicobasal Polarity during Development of the Stratified Xenopus Epidermis

    Science.gov (United States)

    Wang, Sha; Cha, Sang-Wook; Zorn, Aaron M.; Wylie, Christopher

    2013-01-01

    During early vertebrate development, epithelial cells establish and maintain apicobasal polarity, failure of which can cause developmental defects or cancer metastasis. This process has been mostly studied in simple epithelia that have only one layer of cells, but is poorly understood in stratified epithelia. In this paper we address the role of the polarity protein Partitioning defective-6 homolog beta (Par6b) in the developing stratified epidermis of Xenopus laevis. At the blastula stage, animal blastomeres divide perpendicularly to the apicobasal axis to generate partially polarized superficial cells and non-polarized deep cells. Both cell populations modify their apicobasal polarity during the gastrula stage, before differentiating into the superficial and deep layers of epidermis. Early differentiation of the epidermis is normal in Par6b-depleted embryos; however, epidermal cells dissociate and detach from embryos at the tailbud stage. Par6b-depleted epidermal cells exhibit a significant reduction in basolaterally localized E-cadherin. Examination of the apical marker Crumbs homolog 3 (Crb3) and the basolateral marker Lethal giant larvae 2 (Lgl2) after Par6b depletion reveals that Par6b cell-autonomously regulates the dynamics of apicobasal polarity in both superficial and deep epidermal layers. Par6b is required to maintain the “basolateral” state in both epidermal layers, which explains the reduction of basolateral adhesion complexes and epidermal cells shedding. PMID:24204686

  8. Robust Takagi-Sugeno Fuzzy Dynamic Regulator for Trajectory Tracking of a Pendulum-Cart System

    Directory of Open Access Journals (Sweden)

    Miguel A. Llama

    2015-01-01

    Full Text Available Starting from a nonlinear model for a pendulum-cart system, on which viscous friction is considered, a Takagi-Sugeno (T-S fuzzy augmented model (TSFAM as well as a TSFAM with uncertainty (TSFAMwU is proposed. Since the design of a T-S fuzzy controller is based on the T-S fuzzy model of the nonlinear system, then, to address the trajectory tracking problem of the pendulum-cart system, three T-S fuzzy controllers are proposed via parallel distributed compensation: (1 a T-S fuzzy servo controller (TSFSC designed from the TSFAM; (2 a robust TSFSC (RTSFSC designed from the TSFAMwU; and (3 a robust T-S fuzzy dynamic regulator (RTSFDR designed from the RTSFSC with the addition of a T-S fuzzy observer, which estimates cart and pendulum velocities. Both TSFAM and TSFAMwU are comprised of two fuzzy rules and designed via local approximation in fuzzy partition spaces technique. Feedback gains for the three fuzzy controllers are obtained via linear matrix inequalities approach. A swing-up controller is developed to swing the pendulum up from its pendant position to its upright position. Real-time experiments validate the effectiveness of the proposed schemes, keeping the pendulum in its upright position while the cart follows a reference signal, standing out the RTSFDR.

  9. Angiogenin enhances cell migration by regulating stress fiber assembly and focal adhesion dynamics.

    Directory of Open Access Journals (Sweden)

    Saisai Wei

    Full Text Available Angiogenin (ANG acts on both vascular endothelial cells and cancer cells, but the underlying mechanism remains elusive. In this study, we carried out a co-immunoprecipitation assay in HeLa cells and identified 14 potential ANG-interacting proteins. Among these proteins, β-actin, α-actinin 4, and non-muscle myosin heavy chain 9 are stress fiber components and involved in cytoskeleton organization and movement, which prompted us to investigate the mechanism of action of ANG in cell migration. Upon confirmation of the interactions between ANG and the three proteins, further studies revealed that ANG co-localized with β-actin and α-actinin 4 at the leading edge of migrating cells. Down-regulation of ANG resulted in fewer but thicker stress fibers with less dynamics, which was associated with the enlargements of focal adhesions. The focal adhesion kinase activity and cell migration capacity were significantly decreased in ANG-deficient cells. Taken together, our data demonstrated that the existence of ANG in the cytoplasm optimizes stress fiber assembly and focal adhesion formation to accommodate cell migration. The finding that ANG promoted cancer cell migration might provide new clues for tumor metastasis research.

  10. Enhancement of Transient Stability Limit and Voltage Regulation with Dynamic Loads Using Robust Excitation Control

    Science.gov (United States)

    Hossain, Jahangir; Mahmud, Apel; Roy, Naruttam K.; Pota, Hemanshu R.

    2013-10-01

    In stressed power systems with large induction machine component, there exist undamped electromechanical modes and unstable monotonic voltage modes. This article proposes a sequential design of an excitation controller and a power system stabiliser (PSS) to stabilise the system. The operating region, with induction machines in stressed power systems, is often not captured using a linearisation around an operating point, and to alleviate this situation a robust controller is designed which guarantees stable operation in a large region of operation. A minimax linear quadratic Gaussian design is used for the design of the supplementary control to automatic voltage regulators, and a classical PSS structure is used to damp electromechanical oscillations. The novelty of this work is in proposing a method to capture the unmodelled nonlinear dynamics as uncertainty in the design of the robust controller. Tight bounds on the uncertainty are obtained using this method which enables high-performance controllers. An IEEE benchmark test system has been used to demonstrate the performance of the designed controller.

  11. Coiled-Coil Domains of SUN Proteins as Intrinsic Dynamic Regulators.

    Science.gov (United States)

    Nie, Si; Ke, Huimin; Gao, Feng; Ren, Jinqi; Wang, Mingzhu; Huo, Lin; Gong, Weimin; Feng, Wei

    2016-01-05

    SUN proteins are the core components of LINC complexes that span across the nuclear envelope for nuclear positioning and migration. SUN proteins contain at least one predicted coiled-coil domain preceding the SUN domain. Here, we found that the two coiled-coil domains (CC1 and CC2) of SUN2 exhibit distinct oligomeric states. CC2 is a monomer in solution. The structure of the CC2-SUN monomer revealed that CC2 unexpectedly folds as a three-helix bundle that interacts with the SUN domain and locks it in an inactive conformation. In contrast, CC1 is a trimer. The structure of the CC1 trimer demonstrated that CC1 is an imperfect coiled coil for the trimerization and activation of the SUN domain. Modulations of CC1 and CC2 dictate different oligomeric states of CC1-CC2-SUN, which is essential for LINC complex formation. Thus, the two coiled-coil domains of SUN2 act as the intrinsic dynamic regulators for controlling the SUN domain activity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Epidemiological characteristics of multiple sclerosis in Tomsk Region and their dynamics for last 30 years

    Directory of Open Access Journals (Sweden)

    V. M. Alifirova

    2012-01-01

    Full Text Available The Tomsk Region is a zone of average risk multiple sclerosis (MS, prevalence makes 27.1 cases on 100 000 people. During the period with 1980 for 2010 variety of morbidity from 0.4 (1992 to 4.1 (2003 on 100 000 people. The lowest morbidity was in period with 1991 for 1995 and makes 1.8 on 100 000 people, and the highest in the rage from 2001 for 2005 — 3.1 on 100 000 people. Last 5 years in the TomskRegion to increase ofmorbidityis observed.

  13. Target regulation of PI3K/Akt/mTOR pathway by cannabidiol in treatment of experimental multiple sclerosis.

    Science.gov (United States)

    Giacoppo, Sabrina; Pollastro, Federica; Grassi, Gianpaolo; Bramanti, Placido; Mazzon, Emanuela

    2017-01-01

    This study was aimed to investigate whether treatment with purified cannabidiol (CBD) may counteract the development of experimental multiple sclerosis (MS), by targeting the PI3K/Akt/mTOR pathway. Although the PI3K/Akt/mTOR pathway was found to be activated by cannabinoids in several immune and non-immune cells, currently, there is no data about the effects of CBD in the PI3K/Akt/mTOR activity in MS. Experimental Autoimmune Encephalomyelitis (EAE), the most common model of MS, was induced in C57BL/6 mice by immunization with myelin oligodendroglial glycoprotein peptide (MOG) 35-55 . After EAE onset, which occurs approximately 14days after disease induction, mice were daily intraperitoneally treated with CBD (10mg/kg mouse) and observed for clinical signs of EAE. At 28days from EAE-induction, mice were euthanized and spinal cord tissues were sampled to perform immunohistochemical evaluations and western blot analysis. Our results showed a clear downregulation of the PI3K/Akt/mTOR pathway following EAE induction. CBD treatment was able to restore it, increasing significantly the phosphorylation of PI3K, Akt and mTOR. Also, an increased level of BNDF in CBD-treated mice seems to be involved in the activation of PI3K/Akt/mTOR pathway. In addition, our data demonstrated that therapeutic efficacy of CBD treatment is due to reduction of pro-inflammatory cytokines, like IFN-γ and IL-17 together with an up-regulation of PPARγ. Finally, CBD was found to promote neuronal survival by inhibiting JNK and p38 MAP kinases. These results provide an interesting discovery about the regulation of the PI3K/Akt/mTOR pathway by cannabidiol administration, that could be a new potential therapeutic target for MS management. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Multiple length peptide-pheromone variants produced by Streptococcus pyogenes directly bind Rgg proteins to confer transcriptional regulation.

    Science.gov (United States)

    Aggarwal, Chaitanya; Jimenez, Juan Cristobal; Nanavati, Dhaval; Federle, Michael J

    2014-08-08

    Streptococcus pyogenes, a human-restricted pathogen, accounts for substantial mortality related to infections worldwide. Recent studies indicate that streptococci produce and respond to several secreted peptide signaling molecules (pheromones), including those known as short hydrophobic peptides (SHPs), to regulate gene expression by a quorum-sensing mechanism. Upon transport into the bacterial cell, pheromones bind to and modulate activity of receptor proteins belonging to the Rgg family of transcription factors. Previously, we reported biofilm regulation by the Rgg2/3 quorum-sensing circuit in S. pyogenes. The aim of this study was to identify the composition of mature pheromones from cell-free culture supernatants that facilitate biofilm formation. Bioluminescent reporters were employed to detect active pheromones in culture supernatants fractionated by reverse-phase chromatography, and mass spectrometry was used to characterize their properties. Surprisingly, multiple SHPs that varied by length were detected. Synthetic peptides of each variant were tested individually using bioluminescence reporters and biofilm growth assays, and although activities differed widely among the group, peptides comprising the C-terminal eight amino acids of the full-length native peptide were most active. Direct Rgg/SHP interactions were determined using a fluorescence polarization assay that utilized FITC-labeled peptide ligands. Peptide receptor affinities were seen to be as low as 500 nm and their binding affinities directly correlated with observed bioactivity. Revelation of naturally produced pheromones along with determination of their affinity for cognate receptors are important steps forward in designing compounds whose purpose is positioned for future therapeutics aimed at treating infections through the interference of bacterial communication. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. PGC-1α integrates glucose metabolism and angiogenesis in multiple myeloma cells by regulating VEGF and GLUT-4.

    Science.gov (United States)

    Cao, Dedong; Zhou, Hao; Zhao, Jikai; Jin, Lu; Yu, Wen; Yan, Han; Hu, Yu; Guo, Tao

    2014-03-01

    Human peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) is a key coactivator in the regulation of gene transcriptional activity in normal tissues. However, it is not clear whether it is involved in the angiogenesis and metabolism of multiple myeloma (MM). The aim of the present study was to investigate the role of PGC-1α in MM. Small interfering RNA (siRNA) was used to inhibit PGC-1α expression in RPMI-8226 cells. An endothelial cell migration assay was performed using transwell chambers and the expression of PGC-1α, estrogen-related receptor-α (ERR-α), vascular endothelial growth factor (VEGF) and glucose transporter-4 (GLUT-4) was tested by reverse transcription-polymerase chain reaction (RT-PCR). The protein expression of PGC-1α, ERR-α and GLUT-4 was assayed by western blot analysis. Lastly, RPMI-8226 cell proliferation was evaluated using CCK-8 assay. VEGF and GLUT-4 mRNA levels were decreased in cells treated with siRNA targeting PGC-1α, as was the level of GLUT-4 protein. Endothelial cell migration was significantly reduced when these cells were cultured with culture medium from RPMI-8226 cells treated with siPGC-1α. The proliferation rates at 24 and 48 h were suppressed by PGC-1α inhibition. Our results showed that inhibition of PGC-1α suppresses cell proliferation probably by downregulation of VEGF and GLUT-4. The present study suggests that PGC-1α integrates angiogenesis and glucose metabolism in myeloma through regulation of VEGF and GLUT-4.

  16. Neocortical dynamics at multiple scales: EEG standing waves, statistical mechanics, and physical analogs.

    Science.gov (United States)

    Ingber, Lester; Nunez, Paul L

    2011-02-01

    The dynamic behavior of scalp potentials (EEG) is apparently due to some combination of global and local processes with important top-down and bottom-up interactions across spatial scales. In treating global mechanisms, we stress the importance of myelinated axon propagation delays and periodic boundary conditions in the cortical-white matter system, which is topologically close to a spherical shell. By contrast, the proposed local mechanisms are multiscale interactions between cortical columns via short-ranged non-myelinated fibers. A mechanical model consisting of a stretched string with attached nonlinear springs demonstrates the general idea. The string produces standing waves analogous to large-scale coherent EEG observed in some brain states. The attached springs are analogous to the smaller (mesoscopic) scale columnar dynamics. Generally, we expect string displacement and EEG at all scales to result from both global and local phenomena. A statistical mechanics of neocortical interactions (SMNI) calculates oscillatory behavior consistent with typical EEG, within columns, between neighboring columns via short-ranged non-myelinated fibers, across cortical regions via myelinated fibers, and also derives a string equation consistent with the global EEG model. Copyright © 2010 Elsevier Inc. All rights reserved.

  17. An index-based framework for assessing patterns and trends in river fragmentation and flow regulation by global dams at multiple scales

    International Nuclear Information System (INIS)

    Grill, Günther; Lehner, Bernhard; Lumsdon, Alexander E; Zarfl, Christiane; MacDonald, Graham K; Reidy Liermann, Catherine

    2015-01-01

    The global number of dam constructions has increased dramatically over the past six decades and is forecast to continue to rise, particularly in less industrialized regions. Identifying development pathways that can deliver the benefits of new infrastructure while also maintaining healthy and productive river systems is a great challenge that requires understanding the multifaceted impacts of dams at a range of scales. New approaches and advanced methodologies are needed to improve predictions of how future dam construction will affect biodiversity, ecosystem functioning, and fluvial geomorphology worldwide, helping to frame a global strategy to achieve sustainable dam development. Here, we respond to this need by applying a graph-based river routing model to simultaneously assess flow regulation and fragmentation by dams at multiple scales using data at high spatial resolution. We calculated the cumulative impact of a set of 6374 large existing dams and 3377 planned or proposed dams on river connectivity and river flow at basin and subbasin scales by fusing two novel indicators to create a holistic dam impact matrix for the period 1930–2030. Static network descriptors such as basin area or channel length are of limited use in hierarchically nested and dynamic river systems, so we developed the river fragmentation index and the river regulation index, which are based on river volume. These indicators are less sensitive to the effects of network configuration, offering increased comparability among studies with disparate hydrographies as well as across scales. Our results indicate that, on a global basis, 48% of river volume is moderately to severely impacted by either flow regulation, fragmentation, or both. Assuming completion of all dams planned and under construction in our future scenario, this number would nearly double to 93%, largely due to major dam construction in the Amazon Basin. We provide evidence for the importance of considering small to medium

  18. EFFECTS OF PLANT GROWTH REGULATORS ON SHOOT MULTIPLICATION AND ROOT INDUCTION OF CASSAVA VARIETIES CULTURE IN VITRO

    Directory of Open Access Journals (Sweden)

    HERNI WIDHIASTUTI

    2011-01-01

    Full Text Available A study on propagation of three superior cassava ( Crant varieties i.e.Darul Hidayah, Malang-6 and Adira-4 through tissue culture technique was conducted at theTissue Culture Lab of SEAMEO BIOTROP, Bogor. The objective of the experiment was tostudy effect of plant growth regulators on propagation, which can be used in cassavamicropropagation protocol. Plant materials used were auxiliary shoots of a stem node. Theexperiment consisted of (i shoot multiplication, (ii roots induction, and (iii acclimatization.The multiple shoot regeneration was observed by using Murashige & Skoog (MS basal mediasupplemented with 0, 0.1, 1.0 and 5.0 mg/L of benzylaminopurine (BAP combined with 0.0,0.1 and 1.0 mg/L of thidiazuron. The root induction was observed by using 0.1 and 1.0 mg/Lof IBA and NAA. The resulting plantlets were transplanted into plastic polybags containingsoil mixed with organic fertilizer (1:1 covered with plastic sheets and transferred to agreenhouse. The result of the study showed that the highest number of shoots for DarulHidayah, Malang-6 and Adira-4 varieties were 4.93 shoots treated with BAP 1 mg/L +thidiazuron 0.1 mg/L, 4.20 shoots at BAP media of 1 mg/L, and 7.20 shoots at the mediaof BAP 1 mg/L + thidiazuron 0.1 mg/L respectively. The highest number of nodes producedwas 2.9 nodes for Darul Hidayah at BAP 5 mg/L, 5.13 nodes for Malang-6 at BAP 0.1 mg/L,and 6.18 nodes for Adira-4 at BAP 5 mg/L + thidiazuron 1 mg/L. The utilization of auxin IAAor NAA could induce and accelerate the growth of roots which finally could increase thesuccess of acclimatization process. With an average of four multiplication factors of eachculture period, the potency of each cassava shoot propagated through tissue culture couldproduce around 37 000 plants/year.

  19. A memetic algorithm to solve the dynamic multiple runway aircraft landing problem

    Directory of Open Access Journals (Sweden)

    Ghizlane Bencheikh

    2016-01-01

    Full Text Available The aircraft landing problem (ALP consists of scheduling the landing of aircrafts onto the available runways in an airport by assigning to each aircraft a landing time and a specific runway while respecting different operational constraints. This is a complex task for the air traffic controller, especially when the flow of aircrafts entering the radar range is continuous and the number of aircrafts is unknown a priori. In this paper, we study the dynamic version of the ALP when new aircrafts appear over time, which means that the landing of the previous aircrafts should be rescheduled. To solve this problem, we propose a memetic algorithm combining an ant colony algorithm and a local heuristic.

  20. Dynamic biometric identification from multiple views using the GLBP-TOP method.

    Science.gov (United States)

    Wang, Yu; Shen, Xuanjing; Chen, Haipeng; Zhai, Yujie

    2014-01-01

    To realize effective and rapid dynamic biometric identification with low computational complexity, a video-based facial texture program that extracts local binary patterns from three orthogonal planes in the frequency domain of the Gabor transform (GLBP-TOP) was proposed. Firstly, each normalized face was transformed by Gabor wavelet to get the enhanced Gabor magnitude map, and then the LBP-TOP operator was applied to the maps to extract video texture. Finally, weighted Chi square statistics based on the Fisher Criterion were used to realize the identification. The proposed algorithm was proved effective through the biometric experiments using the Honda/UCSD database, and was robust against changes of illumination and expressions.

  1. Dynamics of a mechanical system with multiple degrees of freedom out of thermal equilibrium.

    Science.gov (United States)

    Feigel, A

    2017-05-01

    Out of thermal equilibrium, an environment imposes effective mechanical forces on nanofabricated devices as well as on microscopic chemical or biological systems. Here we address the question of how to calculate these forces together with the response of the system from first principles. We show that an ideal gaslike environment, even near thermal equilibrium, can enforce a specific steady state on the system by creating effective potentials in otherwise homogeneous space. An example of stable and unstable rectifications of thermal fluctuations is presented using a modified Feynman-Smoluchowski ratchet with two degrees of freedom. Moreover, the stability of a steady configuration depends on its chiral symmetry. The transition rate probabilities and the corresponding kinetic equations are derived for a complex mechanical system with arbitrary degrees of freedom. This work, therefore, extends the applicability of mechanical systems as a toy model playground of statistical physics for active and living matter with multiple degrees of freedom.

  2. Dynamic Allocation and Efficient Distribution of Data Among Multiple Clouds Using Network Coding

    DEFF Research Database (Denmark)

    Sipos, Marton A.; Fitzek, Frank; Roetter, Daniel Enrique Lucani

    2014-01-01

    of random linear network coding to exploit multiple commercially available cloud storage providers simultaneously with the possibility to constantly adapt to changing cloud performance in order to optimize data retrieval times. The main contribution of this paper is a new data distribution mechanisms...... that cleverly stores and moves data among different clouds in order to optimize performance. Furthermore, we investigate the trade-offs among storage space, reliability and data retrieval speed for our proposed scheme. By means of real-world implementation and measurements using well-known and publicly...... accessible cloud service providers, we can show close to 9x less network use for the adaptation compared to more conventional dense recoding approaches, while maintaining similar download time performance and the same reliability....

  3. Influence of pollen transport dynamics on sire profiles and multiple paternity in flowering plants.

    Directory of Open Access Journals (Sweden)

    Randall J Mitchell

    Full Text Available In many flowering plants individual fruits contain a mixture of half- and full- siblings, reflecting pollination by several fathers. To better understand the mechanisms generating multiple paternity within fruits we present a theoretical framework linking pollen carryover with patterns of pollinator movement. This 'sire profile' model predicts that species with more extensive pollen carryover will have a greater number of mates. It also predicts that flowers on large displays, which are often probed consecutively during a single pollinator visitation sequence, will have a lower effective number of mates. We compared these predictions with observed values for bumble bee-pollinated Mimulus ringens, which has restricted carryover, and hummingbird-pollinated Ipomopsis aggregata, which has extensive carryover. The model correctly predicted that the effective number of mates is much higher in the species with more extensive carryover. This work extends our knowledge of plant mating systems by highlighting mechanisms influencing the genetic composition of sibships.

  4. Dynamic T-lymphocyte chemokine receptor expression induced by interferon-beta therapy in multiple sclerosis

    DEFF Research Database (Denmark)

    Krakauer, M; Sorensen, P S; Khademi, M

    2006-01-01

    and immunoregulatory genes. In conclusion, IFN-beta treatment caused 'steady-state' increases of several chemokine receptors relevant for CD4(+) T-lymphocyte trafficking and function, possibly facilitating lymphocyte migration into the CNS. An important therapeutic effect of IFN-beta treatment may be the normalization......Treatment with interferon (IFN)-beta reduces clinical disease activity in multiple sclerosis (MS). Using flow cytometry, an enzyme-linked immunosorbent assay and a real-time polymerase chain reaction, we studied in vivo IFN-beta-induced effects on CD4(+) T-lymphocyte chemokine receptor expression...... as these influence central nervous system (CNS) transmigration and inflammation. At 'steady state' (>/=1 day after the most recent IFN-beta injection), IFN-beta treatment increased CD4(+) T-cell surface expression of CC chemokine receptor (CCR)4, CCR5 and CCR7 after 3 months of treatment, whereas that of CXC...

  5. Physiological Mechanisms Only Tell Half Story: Multiple Biological Processes are involved in Regulating Freezing Tolerance of Imbibed Lactuca sativa Seeds.

    Science.gov (United States)

    Jaganathan, Ganesh K; Han, Yingying; Li, Weijie; Song, Danping; Song, Xiaoyan; Shen, Mengqi; Zhou, Qiang; Zhang, Chenxue; Liu, Baolin

    2017-03-13

    The physiological mechanisms by which imbibed seeds survive freezing temperatures in their natural environment have been categorized as freezing avoidance by supercooling and freezing tolerance by extracellular freeze-desiccation, but the biochemical and molecular mechanisms conferring seed freezing tolerance is unexplored. In this study, using imbibed Lactuca sativa seeds we show that fast cooled seeds (60 °C h -1 ) suffered significantly higher membrane damage at temperature between -20 °C and -10 °C than slow cooled (3 °Ch -1 ) seeds (P  0.05). However, both SOD activity and accumulation of free proline were induced significantly after slow cooling to -20 °C compared with fast cooling. RNA-seq demonstrated that multiple pathways were differentially regulated between slow and fast cooling. Real-time verification of some differentially expressed genes (DEGs) revealed that fast cooling caused mRNA level changes of plant hormone and ubiquitionation pathways at higher sub-zero temperature, whilst slow cooling caused mRNA level change of those pathways at lower sub-zero ttemperatures. Thus, we conclude that imbibed seed tolerate low temperature not only by physiological mechanisms but also by biochemical and molecular changes.

  6. Dynamics of multiple viscoelastic carbon nanotube based nanocomposites with axial magnetic field

    International Nuclear Information System (INIS)

    Karličić, Danilo; Cajić, Milan; Murmu, Tony; Kozić, Predrag; Adhikari, Sondipon

    2014-01-01

    Nanocomposites and magnetic field effects on nanostructures have received great attention in recent years. A large amount of research work was focused on developing the proper theoretical framework for describing many physical effects appearing in structures on nanoscale level. Great step in this direction was successful application of nonlocal continuum field theory of Eringen. In the present paper, the free transverse vibration analysis is carried out for the system composed of multiple single walled carbon nanotubes (MSWCNT) embedded in a polymer matrix and under the influence of an axial magnetic field. Equivalent nonlocal model of MSWCNT is adopted as viscoelastically coupled multi-nanobeam system (MNBS) under the influence of longitudinal magnetic field. Governing equations of motion are derived using the Newton second low and nonlocal Rayleigh beam theory, which take into account small-scale effects, the effect of nanobeam angular acceleration, internal damping and Maxwell relation. Explicit expressions for complex natural frequency are derived based on the method of separation of variables and trigonometric method for the “Clamped-Chain” system. In addition, an analytical method is proposed in order to obtain asymptotic damped natural frequency and the critical damping ratio, which are independent of boundary conditions and a number of nanobeams in MNBS. The validity of obtained results is confirmed by comparing the results obtained for complex frequencies via trigonometric method with the results obtained by using numerical methods. The influence of the longitudinal magnetic field on the free vibration response of viscoelastically coupled MNBS is discussed in detail. In addition, numerical results are presented to point out the effects of the nonlocal parameter, internal damping, and parameters of viscoelastic medium on complex natural frequencies of the system. The results demonstrate the efficiency of the suggested methodology to find the closed form

  7. Quantitative transcription dynamic analysis reveals candidate genes and key regulators for ethanol tolerance in Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Ma Menggen

    2010-06-01

    Full Text Available Abstract Background Derived from our lignocellulosic conversion inhibitor-tolerant yeast, we generated an ethanol-tolerant strain Saccharomyces cerevisiae NRRL Y-50316 by enforced evolutionary adaptation. Using a newly developed robust mRNA reference and a master equation unifying gene expression data analyses, we investigated comparative quantitative transcription dynamics of 175 genes selected from previous studies for an ethanol-tolerant yeast and its closely related parental strain. Results A highly fitted master equation was established and applied for quantitative gene expression analyses using pathway-based qRT-PCR array assays. The ethanol-tolerant Y-50316 displayed significantly enriched background of mRNA abundance for at least 35 genes without ethanol challenge compared with its parental strain Y-50049. Under the ethanol challenge, the tolerant Y-50316 responded in consistent expressions over time for numerous genes belonging to groups of heat shock proteins, trehalose metabolism, glycolysis, pentose phosphate pathway, fatty acid metabolism, amino acid biosynthesis, pleiotropic drug resistance gene family and transcription factors. The parental strain showed repressed expressions for many genes and was unable to withstand the ethanol stress and establish a viable culture and fermentation. The distinct expression dynamics between the two strains and their close association with cell growth, viability and ethanol fermentation profiles distinguished the tolerance-response from the stress-response in yeast under the ethanol challenge. At least 82 genes were identified as candidate and key genes for ethanol-tolerance and subsequent fermentation under the stress. Among which, 36 genes were newly recognized by the present study. Most of the ethanol-tolerance candidate genes were found to share protein binding motifs of transcription factors Msn4p/Msn2p, Yap1p, Hsf1p and Pdr1p/Pdr3p. Conclusion Enriched background of transcription abundance

  8. Sexual dimorphic regulation of body weight dynamics and adipose tissue lipolysis.

    Directory of Open Access Journals (Sweden)

    Verena Benz

    Full Text Available BACKGROUND: Successful reduction of body weight (BW is often followed by recidivism to obesity. BW-changes including BW-loss and -regain is associated with marked alterations in energy expenditure (EE and adipose tissue (AT metabolism. Since these processes are sex-specifically controlled, we investigated sexual dimorphisms in metabolic processes during BW-dynamics (gain-loss-regain. RESEARCH DESIGN: Obesity was induced in C57BL/6J male (m and female (f mice by 15 weeks high-fat diet (HFD feeding. Subsequently BW was reduced (-20% by caloric restriction (CR followed by adaptive feeding, and a regain-phase. Measurement of EE, body composition, blood/organ sampling were performed after each feeding period. Lipolysis was analyzed ex-vivo in gonadal AT. RESULTS: Male mice exhibited accelerated BW-gain compared to females (relative BW-gain m:140.5±3.2%; f:103.7±6.5%; p<0.001. In consonance, lean mass-specific EE was significantly higher in females compared to males during BW-gain. Under CR female mice reached their target-BW significantly faster than male mice (m:12.2 days; f:7.6 days; p<0.001 accompanied by a sustained sex-difference in EE. In addition, female mice predominantly downsized gonadal AT whereas the relation between gonadal and total body fat was not altered in males. Accordingly, only females exhibited an increased rate of forskolin-stimulated lipolysis in AT associated with significantly higher glycerol concentrations, lower RER-values, and increased AT expression of adipose triglyceride lipase (ATGL and hormone sensitive lipase (HSL. Analysis of AT lipolysis in estrogen receptor alpha (ERα-deficient mice revealed a reduced lipolytic rate in the absence of ERα exclusively in females. Finally, re-feeding caused BW-regain faster in males than in females. CONCLUSION: The present study shows sex-specific dynamics during BW-gain-loss-regain. Female mice responded to CR with an increase in lipolytic activity, and augmented lipid

  9. A dynamic programming approach for the alignment of signal peaks in multiple gas chromatography-mass spectrometry experiments

    Directory of Open Access Journals (Sweden)

    McConville Malcolm J

    2007-10-01

    Full Text Available Abstract Background Gas chromatography-mass spectrometry (GC-MS is a robust platform for the profiling of certain classes of small molecules in biological samples. When multiple samples are profiled, including replicates of the same sample and/or different sample states, one needs to account for retention time drifts between experiments. This can be achieved either by the alignment of chromatographic profiles prior to peak detection, or by matching signal peaks after they have been extracted from chromatogram data matrices. Automated retention time correction is particularly important in non-targeted profiling studies. Results A new approach for matching signal peaks based on dynamic programming is presented. The proposed approach relies on both peak retention times and mass spectra. The alignment of more than two peak lists involves three steps: (1 all possible pairs of peak lists are aligned, and similarity of each pair of peak lists is estimated; (2 the guide tree is built based on the similarity between the peak lists; (3 peak lists are progressively aligned starting with the two most similar peak lists, following the guide tree until all peak lists are exhausted. When two or more experiments are performed on different sample states and each consisting of multiple replicates, peak lists within each set of replicate experiments are aligned first (within-state alignment, and subsequently the resulting alignments are aligned themselves (between-state alignment. When more than two sets of replicate experiments are present, the between-state alignment also employs the guide tree. We demonstrate the usefulness of this approach on GC-MS metabolic profiling experiments acquired on wild-type and mutant Leishmania mexicana parasites. Conclusion We propose a progressive method to match signal peaks across multiple GC-MS experiments based on dynamic programming. A sensitive peak similarity function is proposed to balance peak retention time and peak

  10. Dynamic Regulation of Cell Volume and Extracellular ATP of Human Erythrocytes.

    Directory of Open Access Journals (Sweden)

    M Florencia Leal Denis

    Full Text Available The peptide mastoparan 7 (MST7 triggered in human erythrocytes (rbcs the release of ATP and swelling. Since swelling is a well-known inducer of ATP release, and extracellular (ATPe, interacting with P (purinergic receptors, can affect cell volume (Vr, we explored the dynamic regulation between Vr and ATPe.We made a quantitative assessment of MST7-dependent kinetics of Vr and of [ATPe], both in the absence and presence of blockers of ATP efflux, swelling and P receptors.In rbcs 10 μM MST7 promoted acute, strongly correlated changes in [ATPe] and Vr. Whereas MST7 induced increases of 10% in Vr and 190 nM in [ATPe], blocking swelling in a hyperosmotic medium + MST7 reduced [ATPe] by 40%. Pre-incubation of rbcs with 10 μM of either carbenoxolone or probenecid, two inhibitors of the ATP conduit pannexin 1, reduced [ATPe] by 40-50% and swelling by 40-60%, while in the presence of 80 U/mL apyrase, an ATPe scavenger, cell swelling was prevented. While exposure to 10 μM NF110, a blocker of ATP-P2X receptors mediating sodium influx, reduced [ATPe] by 48%, and swelling by 80%, incubation of cells in sodium free medium reduced swelling by 92%.Results were analyzed by means of a mathematical model where ATPe kinetics and Vr kinetics were mutually regulated. Model dependent fit to experimental data showed that, upon MST7 exposure, ATP efflux required a fast 1960-fold increase of ATP permeability, mediated by two kinetically different conduits, both of which were activated by swelling and inactivated by time. Both experimental and theoretical results suggest that, following MST7 exposure, ATP is released via two conduits, one of which is mediated by pannexin 1. The accumulated ATPe activates P2X receptors, followed by sodium influx, resulting in cell swelling, which in turn further activates ATP release. Thus swelling and P2X receptors constitute essential components of a positive feedback loop underlying ATP-induced ATP release of rbcs.

  11. Tracking fluid-borne odors in diverse and dynamic environments using multiple sensory mechanisms

    Science.gov (United States)

    Taylor, Brian Kyle

    The ability to locate odor sources in different types of environments (i.e. diverse) and environments that change radically during the mission (i.e., dynamic) is essential. While many engineered odor tracking systems have been developed, they appear to be designed for a particular environment (e.g., strong or low flow). In field conditions, agents may encounter both. Insect olfactory orientation studies show that several animals can locate odor sources in both high and low flow environments, and environments where the wind vanishes during tracking behavior. Furthermore, animals use multi-modal sensing, including olfaction, vision and touch to localize a source. This work uses simulated and hardware environments to explore how engineered systems can maintain wind-driven tracking behavior in diverse and dynamic environments. The simulation uses olfaction, vision and tactile attributes to track and localize a source in the following environments: high flow, low flow, and transition from high to low flow (i.e., Wind Stop). The hardware platform tests two disparate tracking strategies (including the simulated strategy) in an environment that transitions from strong to low flow. Results indicate that using a remembered wind direction post wind-shutoff is a viable way to maintain wind-driven tracking behavior in a wind stop environment, which can help bridge the gap between high flow and low flow strategies. Also, multi-modal sensing with tactile attributes, vision and olfaction helps a vehicle to localize a source. In addition to engineered systems, the moth Manduca sexta is challenged to track in the following environments: Wind and Odor, Wind Stop, Odor and No Wind, No Odor and No Wind to gain a better understanding of animal behavior in these environments. Results show that contrary to previous studies of different moth species, M. sexta does not generally maintain its wind-driven tracking behavior post-wind shutoff, but instead executes a stereotyped sequence of

  12. Improvement of MARS code through the removal of bit-packed words and multiple use of DLLs (Dynamic Link Library)

    International Nuclear Information System (INIS)

    Jung, B. D.; Jung, J. J.; Ha, K. S.; Hwang, M. K.; Lee, Y. S.; Lee, W. J.

    1999-01-01

    The readability of MARS code has been enhanced greatly by replacing the bit-packed word with several logical words and integer words and recoding the related subroutines, which have the complicated bit operations and packed words. Functional improvements of code has been achieved through the multiple uses of dynamic link libraries(DLL) for containment analysis module CONTEMPT4 and multidimensional kinetics analysis module MASTER. The establishment of integrated analysis system, MARS/CONTEMPT/MASTER, was validated through the verification calculation for a postulated problem. MARS user-friendly features are also improved by displaying the 2D contour map of 3 D module data on-line. In addition to the on-line-graphics, the MARS windows menus were upgraded to include the on-line-manual, pre-view of input and output, and link to MARS web site. As a result, the readability, applicability, and user-friendly features of MARS code has been greatly enhanced

  13. Improvement of MARS code through the removal of bit-packed words and multiple use of DLLs (Dynamic Link Library)

    Energy Technology Data Exchange (ETDEWEB)

    Jung, B. D.; Jung, J. J.; Ha, K. S.; Hwang, M. K.; Lee, Y. S.; Lee, W. J. [KAERI, Taejon (Korea, Republic of)

    1999-10-01

    The readability of MARS code has been enhanced greatly by replacing the bit-packed word with several logical words and integer words and recoding the related subroutines, which have the complicated bit operations and packed words. Functional improvements of code has been achieved through the multiple uses of dynamic link libraries(DLL) for containment analysis module CONTEMPT4 and multidimensional kinetics analysis module MASTER. The establishment of integrated analysis system, MARS/CONTEMPT/MASTER, was validated through the verification calculation for a postulated problem. MARS user-friendly features are also improved by displaying the 2D contour map of 3 D module data on-line. In addition to the on-line-graphics, the MARS windows menus were upgraded to include the on-line-manual, pre-view of input and output, and link to MARS web site. As a result, the readability, applicability, and user-friendly features of MARS code has been greatly enhanced.

  14. Profiles of Self-Concept, Goal Orientation, and Self-Regulation in Students with Physical, Intellectual, and Multiple Disabilities: Implications for Instructional Support

    Science.gov (United States)

    Varsamis, Panagiotis; Agaliotis, Ioannis

    2011-01-01

    The present study explored physical self-concept, goal orientation in sport, and self-regulation in regard to a motor task, in 75 secondary students with physical, intellectual, and multiple disabilities, who were educated in the same special education units. It was found that students with intellectual disabilities generally presented a positive…

  15. Artefactual multiplicity

    DEFF Research Database (Denmark)

    Bjørn, Pernille; Hertzum, Morten

    2011-01-01

    Whiteboards are highly important to the work in emergency departments (EDs). As a collaborative technology ED whiteboards are usually placed in the dynamic centre of the ED, and all ED staff will approach the whiteboard regularly to organize their individual yet interdependent work. Currently, di...... this characteristic of heterogeneous artefacts; namely artefactual multiplicity. Artefactual multiplicity identifies not only the multiple functions of heterogeneous artefacts but also the intricate relations between these multiple functionalities....

  16. The impact of multiple information on coupled awareness-epidemic dynamics in multiplex networks

    Science.gov (United States)

    Pan, Yaohui; Yan, Zhijun

    2018-02-01

    Growing interest has emerged in the study of the interplay between awareness and epidemics in multiplex networks. However, previous studies on this issue usually assume that all aware individuals take the same level of precautions, ignoring individual heterogeneity. In this paper, we investigate the coupled awareness-epidemic dynamics in multiplex networks considering individual heterogeneity. Here, the precaution levels are heterogeneous and depend on three types of information: contact information and local and global prevalence information. The results show that contact-based precautions can decrease the epidemic prevalence and augment the epidemic threshold, but prevalence-based precautions, regardless of local or global information, can only decrease the epidemic prevalence. Moreover, unlike previous studies in single-layer networks, we do not find a greater impact of local prevalence information on the epidemic prevalence compared to global prevalence information. In addition, we find that the altruistic behaviors of infected individuals can effectively suppress epidemic spreading, especially when the level of contact-based precaution is high.

  17. Multiple equilibria on planet Dune: climate–vegetation dynamics on a sandy planet

    Directory of Open Access Journals (Sweden)

    Fabio Cresto Aleina

    2013-01-01

    Full Text Available We study the interaction between climate and vegetation on an ideal water-limited planet, focussing on the influence of vegetation on the global water cycle. We introduce a simple mechanistic box model consisting in a two-layer representation of the atmosphere and a two-layer soil scheme. The model includes the dynamics of vegetation cover, and the main physical processes of energy and water exchange among the different components. With a realistic choice of parameters, this model displays three stable equilibria, depending on the initial conditions of soil water and vegetation cover. The system reaches a hot and dry state for low values of initial water content and/or vegetation cover, while we observe a wet, vegetated state with mild surface temperature when the system starts from larger initial values of both variables. The third state is a cold desert, where plants transfer enough water to the atmosphere to start a weaker, evaporation-dominated water cycle before they wilt. These results indicate that in this system vegetation plays a central role in transferring water from the soil to the atmosphere and trigger a hydrologic cycle. The model adopted here can also be used to conceptually illustrate processes and feedbacks affecting the water cycle in water-limited continental areas on Earth.

  18. Utilizing multiple state variables to improve the dynamic range of analog switching in a memristor

    Science.gov (United States)

    Jeong, YeonJoo; Kim, Sungho; Lu, Wei D.

    2015-10-01

    Memristors and memristive systems have been extensively studied for data storage and computing applications such as neuromorphic systems. To act as synapses in neuromorphic systems, the memristor needs to exhibit analog resistive switching (RS) behavior with incremental conductance change. In this study, we show that the dynamic range of the analog RS behavior can be significantly enhanced in a tantalum-oxide-based memristor. By controlling different state variables enabled by different physical effects during the RS process, the gradual filament expansion stage can be selectively enhanced without strongly affecting the abrupt filament length growth stage. Detailed physics-based modeling further verified the observed experimental effects and revealed the roles of oxygen vacancy drift and diffusion processes, and how the diffusion process can be selectively enhanced during the filament expansion stage. These findings lead to more desirable and reliable memristor behaviors for analog computing applications. Additionally, the ability to selectively control different internal physical processes demonstrated in the current study provides guidance for continued device optimization of memristor devices in general.

  19. Accurate discrimination of conserved coding and non-coding regions through multiple indicators of evolutionary dynamics

    Directory of Open Access Journals (Sweden)

    Pesole Graziano

    2009-09-01

    Full Text Available Abstract Background The conservation of sequences between related genomes has long been recognised as an indication of functional significance and recognition of sequence homology is one of the principal approaches used in the annotation of newly sequenced genomes. In the context of recent findings that the number non-coding transcripts in higher organisms is likely to be much higher than previously imagined, discrimination between conserved coding and non-coding sequences is a topic of considerable interest. Additionally, it should be considered desirable to discriminate between coding and non-coding conserved sequences without recourse to the use of sequence similarity searches of protein databases as such approaches exclude the identification of novel conserved proteins without characterized homologs and may be influenced by the presence in databases of sequences which are erroneously annotated as coding. Results Here we present a machine learning-based approach for the discrimination of conserved coding sequences. Our method calculates various statistics related to the evolutionary dynamics of two aligned sequences. These features are considered by a Support Vector Machine which designates the alignment coding or non-coding with an associated probability score. Conclusion We show that our approach is both sensitive and accurate with respect to comparable methods and illustrate several situations in which it may be applied, including the identification of conserved coding regions in genome sequences and the discrimination of coding from non-coding cDNA sequences.

  20. Investigating the Dynamics of Supine Fluid Redistribution Within Multiple Body Segments Between Men and Women.

    Science.gov (United States)

    Yadollahi, Azadeh; Singh, B; Bradley, T Douglas

    2015-09-01

    While supine, fluid moves from the legs and accumulates in the chest and neck. However, patterns of rostral fluid shift are not clear. Furthermore, real-time measurement of neck fluid volume has not been investigated. The objective of this study was to investigate the dynamics of rostral fluid shift in men and women. We developed a bioelectrical impedance system to measure leg, abdominal, thoracic and neck fluid volumes (LFV, AFV, TFV, NFV) continuously. Forty healthy non-obese adults (20 men) lay supine for 90 min while fluid volumes were measured. After 90 min, a similar volume of fluid shifted out of the legs in both sexes (p = 0.079), but men accumulated more fluid in their thorax (63 ± 6 vs. 44 ± 11 ml, p = 0.016) and neck (17 ± 2 vs. 14 ± 1 ml, p = 0.029) than women. In both sexes, the increase in NFV caused a significant increase in neck circumference, which was greater in men (p = 0.009). Furthermore, 80% of rostral fluid shift would occur in the first 2 h of lying supine. These results suggest that greater fluid shift into the thorax and neck may contribute to the higher prevalence of sleep apnea in men than in women.

  1. Examining the Dynamic Structure of Daily Internalizing and Externalizing Behavior at Multiple Levels of Analysis

    Directory of Open Access Journals (Sweden)

    Aidan G.C. Wright

    2015-12-01

    Full Text Available Psychiatric diagnostic covariation suggests that the underlying structure of psychopathology is not one of circumscribed disorders. Quantitative modeling of individual differences in diagnostic patterns has uncovered several broad domains of mental disorder liability, of which the Internalizing and Externalizing spectra have garnered the greatest support. These dimensions have generally been estimated from lifetime or past-year comorbidity patters, which are distal from the covariation of symptoms and maladaptive behavior that ebb and flow in daily life. In this study, structural models are applied to daily diary data (Median = 94 days of maladaptive behaviors collected from a sample (N = 101 of individuals diagnosed with personality disorders. Using multilevel and unified structural equation modeling, between-person, within-person, and person-specific structures were estimated from 16 behaviors that are encompassed by the Internalizing and Externalizing spectra. At the between-person level (i.e., individual differences in average endorsement across days we found support for a two-factor Internalizing-Externalizing model, which exhibits significant associations with corresponding diagnostic spectra. At the within-person level (i.e., dynamic covariation among daily behavior pooled across individuals we found support for a more differentiated, four-factor, Negative Affect-Detachment-Hostility-Impulsivity structure. Finally, we demonstrate that the person-specific structures of associations between these four domains are highly idiosyncratic.

  2. DMPD: The Lps locus: genetic regulation of host responses to bacteriallipopolysaccharide. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 10669111 The Lps locus: genetic regulation of host responses to bacteriallipopolysaccharide. Qur...e The Lps locus: genetic regulation of host responses to bacteriallipopolysaccharide. Authors Qur

  3. Empirical Modeling of Planetary Boundary Layer Dynamics Under Multiple Precipitation Scenarios Using a Two-Layer Soil Moisture Approach: An Example From a Semiarid Shrubland

    Science.gov (United States)

    Sanchez-Mejia, Zulia Mayari; Papuga, Shirley A.

    2017-11-01

    In semiarid regions, where water resources are limited and precipitation dynamics are changing, understanding land surface-atmosphere interactions that regulate the coupled soil moisture-precipitation system is key for resource management and planning. We present a modeling approach to study soil moisture and albedo controls on planetary boundary layer height (PBLh). We used Santa Rita Creosote Ameriflux and Tucson Airport atmospheric sounding data to generate empirical relationships between soil moisture, albedo, and PBLh. Empirical relationships showed that ˜50% of the variation in PBLh can be explained by soil moisture and albedo with additional knowledge gained by dividing the soil profile into two layers. Therefore, we coupled these empirical relationships with soil moisture estimated using a two-layer bucket approach to model PBLh under six precipitation scenarios. Overall we observed that decreases in precipitation tend to limit the recovery of the PBL at the end of the wet season. However, increases in winter precipitation despite decreases in summer precipitation may provide opportunities for positive feedbacks that may further generate more winter precipitation. Our results highlight that the response of soil moisture, albedo, and the PBLh will depend not only on changes in annual precipitation, but also on the frequency and intensity of this change. We argue that because albedo and soil moisture data are readily available at multiple temporal and spatial scales, developing empirical relationships that can be used in land surface-atmosphere applications have great potential for exploring the consequences of climate change.

  4. DMPD: Iron regulation of hepatic macrophage TNFalpha expression. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 11841920 Iron regulation of hepatic macrophage TNFalpha expression. Tsukamoto H. Fr...ee Radic Biol Med. 2002 Feb 15;32(4):309-13. (.png) (.svg) (.html) (.csml) Show Iron regulation of hepatic m...acrophage TNFalpha expression. PubmedID 11841920 Title Iron regulation of hepatic macrophage TNFalpha expres

  5. DMPD: New insights into NF-kappaB regulation and function. [Dynamic Macrophage Pathway CSML Database

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    Full Text Available 18775672 New insights into NF-kappaB regulation and function. Sun SC, Ley SC. Trend...s Immunol. 2008 Oct;29(10):469-78. Epub 2008 Sep 3. (.png) (.svg) (.html) (.csml) Show New insights into NF-...kappaB regulation and function. PubmedID 18775672 Title New insights into NF-kappaB regulation and function.

  6. DMPD: Interferon gene regulation: not all roads lead to Tolls. [Dynamic Macrophage Pathway CSML Database

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    Full Text Available 16095970 Interferon gene regulation: not all roads lead to Tolls. Jefferies CA, Fit...zgerald KA. Trends Mol Med. 2005 Sep;11(9):403-11. (.png) (.svg) (.html) (.csml) Show Interferon gene regulation: not all roads lead... to Tolls. PubmedID 16095970 Title Interferon gene regulation: not all roads lead to

  7. DMPD: Toll-like receptors regulation of viral infection and disease. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18280610 Toll-like receptors regulation of viral infection and disease. Thompson JM...how Toll-like receptors regulation of viral infection and disease. PubmedID 18280610 Title Toll-like recepto...rs regulation of viral infection and disease. Authors Thompson JM, Iwasaki A. Pub

  8. DMPD: Innate immune recognition of, and regulation by, DNA. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 16979939 Innate immune recognition of, and regulation by, DNA. Ishii KJ, Akira S. T...rends Immunol. 2006 Nov;27(11):525-32. Epub 2006 Sep 18. (.png) (.svg) (.html) (.csml) Show Innate immune reco...gnition of, and regulation by, DNA. PubmedID 16979939 Title Innate immune recognition of, and regulation b

  9. DMPD: Negative regulation of cytoplasmic RNA-mediated antiviral signaling. [Dynamic Macrophage Pathway CSML Database

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    Full Text Available 18703349 Negative regulation of cytoplasmic RNA-mediated antiviral signaling. Komur...Show Negative regulation of cytoplasmic RNA-mediated antiviral signaling. PubmedID 18703349 Title Negative r...egulation of cytoplasmic RNA-mediated antiviral signaling. Authors Komuro A, Bamm

  10. DMPD: New insights into the regulation of TLR signaling. [Dynamic Macrophage Pathway CSML Database

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    Full Text Available 16698941 New insights into the regulation of TLR signaling. Miggin SM, O'Neill LA. ...J Leukoc Biol. 2006 Aug;80(2):220-6. Epub 2006 May 12. (.png) (.svg) (.html) (.csml) Show New insights into the regulation of TLR sig...naling. PubmedID 16698941 Title New insights into the regulation of TLR signaling.

  11. DMPD: Regulation of mitochondrial antiviral signaling pathways. [Dynamic Macrophage Pathway CSML Database

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    Full Text Available 18549796 Regulation of mitochondrial antiviral signaling pathways. Moore CB, Ting J...P. Immunity. 2008 Jun;28(6):735-9. (.png) (.svg) (.html) (.csml) Show Regulation of mitochondrial antiviral signaling pathways.... PubmedID 18549796 Title Regulation of mitochondrial antiviral signaling pathways. Author

  12. DMPD: Regulation of endogenous apolipoprotein E secretion by macrophages. [Dynamic Macrophage Pathway CSML Database

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    Full Text Available 18388328 Regulation of endogenous apolipoprotein E secretion by macrophages. Kockx ...svg) (.html) (.csml) Show Regulation of endogenous apolipoprotein E secretion by macrophages. PubmedID 18388...328 Title Regulation of endogenous apolipoprotein E secretion by macrophages. Aut

  13. DMPD: Post-transcriptional regulation of proinflammatory proteins. [Dynamic Macrophage Pathway CSML Database

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    Full Text Available 15075353 Post-transcriptional regulation of proinflammatory proteins. Anderson P, P...l) (.csml) Show Post-transcriptional regulation of proinflammatory proteins. PubmedID 15075353 Title Post-tr...anscriptional regulation of proinflammatory proteins. Authors Anderson P, Phillip

  14. DMPD: Regulation of cytokine signaling by SOCS family molecules. [Dynamic Macrophage Pathway CSML Database

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    Full Text Available 14644140 Regulation of cytokine signaling by SOCS family molecules. Fujimoto M, Nak...a T. Trends Immunol. 2003 Dec;24(12):659-66. (.png) (.svg) (.html) (.csml) Show Regulation of cytokine signaling by SOCS family... molecules. PubmedID 14644140 Title Regulation of cytokine signaling by SOCS family molec

  15. DMPD: The SAP family of adaptors in immune regulation. [Dynamic Macrophage Pathway CSML Database

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    Full Text Available 15541655 The SAP family of adaptors in immune regulation. Latour S, Veillette A. Se...min Immunol. 2004 Dec;16(6):409-19. (.png) (.svg) (.html) (.csml) Show The SAP family of adaptors in immune ...regulation. PubmedID 15541655 Title The SAP family of adaptors in immune regulation. Authors Latour S, Veill

  16. DMPD: Innate immune responses: crosstalk of signaling and regulation of genetranscription. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 16753195 Innate immune responses: crosstalk of signaling and regulation of genetran...l) (.csml) Show Innate immune responses: crosstalk of signaling and regulation of genetranscription. PubmedI...D 16753195 Title Innate immune responses: crosstalk of signaling and regulation o

  17. A Novel Randomized Search Technique for Multiple Mobile Robot Paths Planning In Repetitive Dynamic Environment

    Directory of Open Access Journals (Sweden)

    Vahid Behravesh

    2012-08-01

    Full Text Available Presented article is studying the issue of path navigating for numerous robots. Our presented approach is based on both priority and the robust method for path finding in repetitive dynamic. Presented model can be generally implementable and useable: We do not assume any restriction regarding the quantity of levels of freedom for robots, and robots of diverse kinds can be applied at the same time. We proposed a random method and hill-climbing technique in the area based on precedence plans, which is used to determine a solution to a given trajectory planning problem and to make less the extent of total track. Our method plans trajectories for particular robots in the setting-time scope. Therefore, in order to specifying the interval of constant objects similar to other robots and the extent of the tracks which is traversed. For measuring the hazard for robots to conflict with each other it applied a method based on probability of the movements of robots. This algorithm applied to real robots with successful results. The proposed method performed and judged on both real robots and in simulation. We performed sequence of100tests with 8 robots for comparing with coordination method and current performances are effective. However, maximizing the performance is still possible. These performances estimations performed on Windows operating system and 3GHz Intel Pentium IV with and compiles with GCC 3.4. We used our PCGA robot for all experiments.  For a large environment of 19×15m2where we accomplished 40tests, our model is competent to plan high-quality paths in a severely short time (less than a second. Moreover, this article utilized lookup tables to keep expenses the formerly navigated robots made, increasing the number of robots don’t expand computation time.

  18. THE LONG-TERM DYNAMICAL EVOLUTION OF DISK-FRAGMENTED MULTIPLE SYSTEMS IN THE SOLAR NEIGHBORHOOD

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yun [Department of Astronomy, School of Physics, Peking University, Yiheyuan Lu 5, Haidian Qu, Beijing 100871 (China); Kouwenhoven, M. B. N. [Department of Mathematical Sciences, Xi’an Jiaotong-Liverpool University, 111 Ren’ai Road, Suzhou Dushu Lake Science and Education Innovation District, Suzhou Industrial Park, Suzhou 215123 (China); Stamatellos, D. [Jeremiah Horrocks Institute for Mathematics, Physics and Astronomy, University of Central Lancashire, Preston PR1 2HE (United Kingdom); Goodwin, Simon P., E-mail: t.kouwenhoven@xjtlu.edu.cn [Department of Physics and Astronomy, The University of Sheffield, Hicks Building, Hounsfield Road, Sheffield S3 7RH (United Kingdom)

    2016-11-10

    The origin of very low-mass hydrogen-burning stars, brown dwarfs (BDs), and planetary-mass objects (PMOs) at the low-mass end of the initial mass function is not yet fully understood. Gravitational fragmentation of circumstellar disks provides a possible mechanism for the formation of such low-mass objects. The kinematic and binary properties of very low-mass objects formed through disk fragmentation at early times (<10 Myr) were discussed in our previous paper. In this paper we extend the analysis by following the long-term evolution of disk-fragmented systems up to an age of 10 Gyr, covering the ages of the stellar and substellar populations in the Galactic field. We find that the systems continue to decay, although the rates at which companions escape or collide with each other are substantially lower than during the first 10 Myr, and that dynamical evolution is limited beyond 1 Gyr. By t = 10 Gyr, about one third of the host stars are single, and more than half have only one companion left. Most of the other systems have two companions left that orbit their host star in widely separated orbits. A small fraction of companions have formed binaries that orbit the host star in a hierarchical triple configuration. The majority of such double-companion systems have internal orbits that are retrograde with respect to their orbits around their host stars. Our simulations allow a comparison between the predicted outcomes of disk fragmentation with the observed low-mass hydrogen-burning stars, BDs, and PMOs in the solar neighborhood. Imaging and radial velocity surveys for faint binary companions among nearby stars are necessary for verification or rejection of the formation mechanism proposed in this paper.

  19. Investigating water budget dynamics in 18 river basins across the Tibetan Plateau through multiple datasets

    Science.gov (United States)

    Liu, Wenbin; Sun, Fubao; Li, Yanzhong; Zhang, Guoqing; Sang, Yan-Fang; Lim, Wee Ho; Liu, Jiahong; Wang, Hong; Bai, Peng

    2018-01-01

    The dynamics of basin-scale water budgets over the Tibetan Plateau (TP) are not well understood nowadays due to the lack of in situ hydro-climatic observations. In this study, we investigate the seasonal cycles and trends of water budget components (e.g. precipitation P, evapotranspiration ET and runoff Q) in 18 TP river basins during the period 1982-2011 through the use of multi-source datasets (e.g. in situ observations, satellite retrievals, reanalysis outputs and land surface model simulations). A water balance-based two-step procedure, which considers the changes in basin-scale water storage on the annual scale, is also adopted to calculate actual ET. The results indicated that precipitation (mainly snowfall from mid-autumn to next spring), which are mainly concentrated during June-October (varied among different monsoons-impacted basins), was the major contributor to the runoff in TP basins. The P, ET and Q were found to marginally increase in most TP basins during the past 30 years except for the upper Yellow River basin and some sub-basins of Yalong River, which were mainly affected by the weakening east Asian monsoon. Moreover, the aridity index (PET/P) and runoff coefficient (Q/P) decreased slightly in most basins, which were in agreement with the warming and moistening climate in the Tibetan Plateau. The results obtained demonstrated the usefulness of integrating multi-source datasets to hydrological applications in the data-sparse regions. More generally, such an approach might offer helpful insights into understanding the water and energy budgets and sustainability of water resource management practices of data-sparse regions in a changing environment.

  20. Multiple degree of freedom inverted pendulum dynamics: Modeling, computation, and experimentation

    Science.gov (United States)

    Chen, Cheng-Yuan Jerry

    A pendulum is statically unstable in its upright inverted state due to the Earth's gravitational attraction which points downward. However, with proper forcing, the pendulum can be stabilized in its upright inverted state. Special interest is on periodic vertical forcing applied to the pendulum's base to stabilize it around the upright inverted equilibrium. Many researchers have studied how to stabilize the system by varying various parameters, in particular its amplitude and frequency. Most have focused on the single degree of freedom inverted pendulum case, which with linear assumption can be described via Mathieu's equation. The system stability can then be characterized by Floquet theory. Our focus is on searching for the periodic solutions inside the linearly stable region of the pendulum's inverted state when the pendulum is under proper periodic forcing. Our research shows that under appropriate excitation by controlling the forcing amplitude and frequency, the pendulum can maintain certain periodic orbits around its inverted state which we characterize in a systematic way. In this thesis, we applied four different kinds of geometric realizations of the system response: system time traces, system phase portraits, three dimensional views of the system phase portrait as a function of input forcing, and the system's power spectral density diagram. By analyzing these four diagrams simultaneously, we characterize different kinds of multi-frequency periodic behavior around the pendulum's inverted state. To further discuss the effect of the nonlinearity, we applied perturbation techniques using the normalized forcing amplitude as a perturbation parameter to carry out the approximate periodic solutions on a single degree of freedom inverted pendulum nonlinear model. We also discuss the multiple degree of freedom inverted pendulum system. Both numerical simulation and experiments were performed and detailed comparisons are discussed. Our numerical simulations show

  1. Profiles of self-concept, goal orientation, and self-regulation in students with physical, intellectual, and multiple disabilities: Implications for instructional support.

    Science.gov (United States)

    Varsamis, Panagiotis; Agaliotis, Ioannis

    2011-01-01

    The present study explored physical self-concept, goal orientation in sport, and self-regulation in regard to a motor task, in 75 secondary students with physical, intellectual, and multiple disabilities, who were educated in the same special education units. It was found that students with intellectual disabilities generally presented a positive profile in all three psychosocial constructs, whereas students with physical disabilities presented low scores in most measures. Students with multiple disabilities did not differ essentially from students with intellectual disability in regard to physical self-concept and goal orientation; however, they compared unfavorably to them regarding self-regulation. The delineation of a distinct and defendable profile of self-concept, goal orientation, and self-regulation for each disability group allows the formulation of proposals for the implementation of appropriate instructional programs for students belonging to the above mentioned categories. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. Model of Dynamic Pricing for Two Parallels Flights with Multiple Fare Classes Based on Passenger Choice Behavior

    Directory of Open Access Journals (Sweden)

    Ahmad Rusdiansyah

    2010-01-01

    Full Text Available Airline revenue management (ARM is one of emerging topics in transportation logistics areas. This paper discusses a problem in ARM which is dynamic pricing for two parallel flights owned by the same airline. We extended the existing model on Joint Pricing Model for Parallel Flights under passenger choice behavior in the literature. We generalized the model to consider multiple full-fare class instead of only single full-fare class. Consequently, we have to define the seat allocation for each fare class beforehand. We have combined the joint pricing model and the model of nested Expected Marginal Seat Revenue (EMSR model. To solve this hybrid model, we have developed a dynamic programming-based algorithm. We also have conducted numerical experiments to show the behavior of our model. Our experiment results have showed that the expected revenue of both flights significantly induced by the proportion of the time flexible passengers and the number of allocated seat in each full-fare class. As managerial insights, our model has proved that there is a closed relationship between demand management, which is represented by the price of each fare class, and total expected revenue considering the passenger choice behavior.

  3. New Evidence for the Dynamical Decay of a Multiple System in the Orion Kleinmann–Low Nebula

    Energy Technology Data Exchange (ETDEWEB)

    Luhman, K. L. [Department of Astronomy and Astrophysics, The Pennsylvania State University, University Park, PA 16802 (United States); Robberto, M.; Gabellini, M. Giulia Ubeira; Ubeda, L. [Space Telescope Science Institute, 3700 San Martin Drive, Baltimore, MD 21218 (United States); Tan, J. C. [Department of Astronomy, University of Florida, Gainesville, FL 32611 (United States); Andersen, M. [Gemini Observatory, Casilla 603, La Serena (Chile); Manara, C. F. [Scientific Support Office, Directorate of Science, European Space Research and Technology Centre, Keplerlaan 1, NL-2201 AZ Noordwijk (Netherlands); Platais, I., E-mail: kluhman@astro.psu.edu [Johns Hopkins University, Department of Physics and Astronomy, 3400 North Charles Street, Baltimore, MD 21218 (United States)

    2017-03-20

    We have measured astrometry for members of the Orion Nebula Cluster with images obtained in 2015 with the Wide Field Camera 3 on board the Hubble Space Telescope . By comparing those data to previous measurements with the Near-Infrared Camera and Multi-Object Spectrometer on Hubble in 1998, we have discovered that a star in the Kleinmann–Low Nebula, source x from Lonsdale et al., is moving with an unusually high proper motion of 29 mas yr{sup −1}, which corresponds to 55 km s{sup −1} at the distance of Orion. Previous radio observations have found that three other stars in the Kleinmann–Low Nebula (the Becklin–Neugebauer object and sources I and n) have high proper motions (5–14 mas yr{sup −1}) and were near a single location ∼540 years ago, and thus may have been members of a multiple system that dynamically decayed. The proper motion of source x is consistent with ejection from that same location 540 years ago, which provides strong evidence that the dynamical decay did occur and that the runaway star BN originated in the Kleinmann–Low Nebula rather than the nearby Trapezium cluster. However, our constraint on the motion of source n is significantly smaller than the most recent radio measurement, which indicates that it did not participate in the event that ejected the other three stars.

  4. Improving Regional Dynamic Downscaling with Multiple Linear Regression Model Using Components Principal Analysis: Precipitation over Amazon and Northeast Brazil

    Directory of Open Access Journals (Sweden)

    Aline Gomes da Silva

    2014-01-01

    Full Text Available In the current context of climate change discussions, predictions of future scenarios of weather and climate are crucial for the generation of information of interest to the global community. Due to the atmosphere being a chaotic system, errors in predictions of future scenarios are systematically observed. Therefore, numerous techniques have been tested in order to generate more reliable predictions, and two techniques have excelled in science: dynamic downscaling, through regional models, and ensemble prediction, combining different outputs of climate models through the arithmetic average, in other words, a postprocessing of the output data species. Thus, this paper proposes a method of postprocessing outputs of regional climate models. This method consists in using the statistical tool multiple linear regression by principal components for combining different simulations obtained by dynamic downscaling with the regional climate model (RegCM4. Tests for the Amazon and Northeast region of Brazil (South America showed that the method provided a more realistic prediction in terms of average daily rainfall for the analyzed period prescribed, after comparing with the prediction made by set through the arithmetic averages of the simulations. This method photographed the extreme events (outlier that the prediction by averaging failed. Data from the Tropical Rainfall Measuring Mission (TRMM were used to evaluate the method.

  5. [Dynamics of health and aging rate of patients of different age and sex in the treatment of moderate multiple pathologies].

    Science.gov (United States)

    Myakotnykh, V S; Gavrilov, I V; Egorin, K V; Meshchaninov, V N; Borovkova, T A

    2013-01-01

    The article presents results of investigation of the dynamics of health status of patients of different age and sex, with several non-serious diseases, in the course of their treatment in the hospital, as well as the determination of their biological age before and after the course of treatment. The clear differences in the number of diseases, their nature, duration of the treatment and its effectiveness depending on age and sex were revealed. However, at the age of older than 60 years these differences gradually disappearing. Multiple, although non-serious, pathology has a negative impact on the indicators of the biological age of men in the calendar age of 20-39 years and women in the calendar age of 20-39 and older than 60 years, but the rejuvenating effect of the treatment is extremely low. In a number of cases, in the process of treatment of multiple pathologies the indicators of initially reduced biological age get even higher and adapt to the indicators of the calendar age. The authors explain this from the position of the disturbed by the treatment adaptation of the organism to easy disease, as well as the opportunity of reviewing the biological age significantly reduced in relation to the calendar age as a pathological phenomenon similar to significantly increased biological age.

  6. Comparing results from multiple imputation and dynamic marginal structural models for estimating when to start antiretroviral therapy.

    Science.gov (United States)

    Shepherd, Bryan E; Liu, Qi; Mercaldo, Nathaniel; Jenkins, Cathy A; Lau, Bryan; Cole, Stephen R; Saag, Michael S; Sterling, Timothy R

    2016-10-30

    Optimal timing of initiating antiretroviral therapy has been a controversial topic in HIV research. Two highly publicized studies applied different analytical approaches, a dynamic marginal structural model and a multiple imputation method, to different observational databases and came up with different conclusions. Discrepancies between the two studies' results could be due to differences between patient populations, fundamental differences between statistical methods, or differences between implementation details. For example, the two studies adjusted for different covariates, compared different thresholds, and had different criteria for qualifying measurements. If both analytical approaches were applied to the same cohort holding technical details constant, would their results be similar? In this study, we applied both statistical approaches using observational data from 12,708 HIV-infected persons throughout the USA. We held technical details constant between the two methods and then repeated analyses varying technical details to understand what impact they had on findings. We also present results applying both approaches to simulated data. Results were similar, although not identical, when technical details were held constant between the two statistical methods. Confidence intervals for the dynamic marginal structural model tended to be wider than those from the imputation approach, although this may have been due in part to additional external data used in the imputation analysis. We also consider differences in the estimands, required data, and assumptions of the two statistical methods. Our study provides insights into assessing optimal dynamic treatment regimes in the context of starting antiretroviral therapy and in more general settings. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  7. Modeling the potential effects of new tobacco products and policies: a dynamic population model for multiple product use and harm.

    Directory of Open Access Journals (Sweden)

    Eric D Vugrin

    Full Text Available Recent declines in US cigarette smoking prevalence have coincided with increases in use of other tobacco products. Multiple product tobacco models can help assess the population health impacts associated with use of a wide range of tobacco products.We present a multi-state, dynamical systems population structure model that can be used to assess the effects of tobacco product use behaviors on population health. The model incorporates transition behaviors, such as initiation, cessation, switching, and dual use, related to the use of multiple products. The model tracks product use prevalence and mortality attributable to tobacco use for the overall population and by sex and age group. The model can also be used to estimate differences in these outcomes between scenarios by varying input parameter values. We demonstrate model capabilities by projecting future cigarette smoking prevalence and smoking-attributable mortality and then simulating the effects of introduction of a hypothetical new lower-risk tobacco product under a variety of assumptions about product use. Sensitivity analyses were conducted to examine the range of population impacts that could occur due to differences in input values for product use and risk. We demonstrate that potential benefits from cigarette smokers switching to the lower-risk product can be offset over time through increased initiation of this product. Model results show that population health benefits are particularly sensitive to product risks and initiation, switching, and dual use behaviors.Our model incorporates the variety of tobacco use behaviors and risks that occur with multiple products. As such, it can evaluate the population health impacts associated with the introduction of new tobacco products or policies that may result in product switching or dual use. Further model development will include refinement of data inputs for non-cigarette tobacco products and inclusion of health outcomes such as morbidity

  8. Modeling the Potential Effects of New Tobacco Products and Policies: A Dynamic Population Model for Multiple Product Use and Harm

    Science.gov (United States)

    Vugrin, Eric D.; Rostron, Brian L.; Verzi, Stephen J.; Brodsky, Nancy S.; Brown, Theresa J.; Choiniere, Conrad J.; Coleman, Blair N.; Paredes, Antonio; Apelberg, Benjamin J.

    2015-01-01

    Background Recent declines in US cigarette smoking prevalence have coincided with increases in use of other tobacco products. Multiple product tobacco models can help assess the population health impacts associated with use of a wide range of tobacco products. Methods and Findings We present a multi-state, dynamical systems population structure model that can be used to assess the effects of tobacco product use behaviors on population health. The model incorporates transition behaviors, such as initiation, cessation, switching, and dual use, related to the use of multiple products. The model tracks product use prevalence and mortality attributable to tobacco use for the overall population and by sex and age group. The model can also be used to estimate differences in these outcomes between scenarios by varying input parameter values. We demonstrate model capabilities by projecting future cigarette smoking prevalence and smoking-attributable mortality and then simulating the effects of introduction of a hypothetical new lower-risk tobacco product under a variety of assumptions about product use. Sensitivity analyses were conducted to examine the range of population impacts that could occur due to differences in input values for product use and risk. We demonstrate that potential benefits from cigarette smokers switching to the lower-risk product can be offset over time through increased initiation of this product. Model results show that population health benefits are particularly sensitive to product risks and initiation, switching, and dual use behaviors. Conclusion Our model incorporates the variety of tobacco use behaviors and risks that occur with multiple products. As such, it can evaluate the population health impacts associated with the introduction of new tobacco products or policies that may result in product switching or dual use. Further model development will include refinement of data inputs for non-cigarette tobacco products and inclusion of health

  9. Modeling the potential effects of new tobacco products and policies: a dynamic population model for multiple product use and harm.

    Science.gov (United States)

    Vugrin, Eric D; Rostron, Brian L; Verzi, Stephen J; Brodsky, Nancy S; Brown, Theresa J; Choiniere, Conrad J; Coleman, Blair N; Paredes, Antonio; Apelberg, Benjamin J

    2015-01-01

    Recent declines in US cigarette smoking prevalence have coincided with increases in use of other tobacco products. Multiple product tobacco models can help assess the population health impacts associated with use of a wide range of tobacco products. We present a multi-state, dynamical systems population structure model that can be used to assess the effects of tobacco product use behaviors on population health. The model incorporates transition behaviors, such as initiation, cessation, switching, and dual use, related to the use of multiple products. The model tracks product use prevalence and mortality attributable to tobacco use for the overall population and by sex and age group. The model can also be used to estimate differences in these outcomes between scenarios by varying input parameter values. We demonstrate model capabilities by projecting future cigarette smoking prevalence and smoking-attributable mortality and then simulating the effects of introduction of a hypothetical new lower-risk tobacco product under a variety of assumptions about product use. Sensitivity analyses were conducted to examine the range of population impacts that could occur due to differences in input values for product use and risk. We demonstrate that potential benefits from cigarette smokers switching to the lower-risk product can be offset over time through increased initiation of this product. Model results show that population health benefits are particularly sensitive to product risks and initiation, switching, and dual use behaviors. Our model incorporates the variety of tobacco use behaviors and risks that occur with multiple products. As such, it can evaluate the population health impacts associated with the introduction of new tobacco products or policies that may result in product switching or dual use. Further model development will include refinement of data inputs for non-cigarette tobacco products and inclusion of health outcomes such as morbidity and disability.

  10. Bidirectional coupling between astrocytes and neurons mediates learning and dynamic coordination in the brain: a multiple modeling approach.

    Directory of Open Access Journals (Sweden)

    John J Wade

    Full Text Available In recent years research suggests that astrocyte networks, in addition to nutrient and waste processing functions, regulate both structural and synaptic plasticity. To understand the biological mechanisms that underpin such plasticity requires the development of cell level models that capture the mutual interaction between astrocytes and neurons. This paper presents a detailed model of bidirectional signaling between astrocytes and neurons (the astrocyte-neuron model or AN model which yields new insights into the computational role of astrocyte-neuronal coupling. From a set of modeling studies we demonstrate two significant findings. Firstly, that spatial signaling via astrocytes can relay a "learning signal" to remote synaptic sites. Results show that slow inward currents cause synchronized postsynaptic activity in remote neurons and subsequently allow Spike-Timing-Dependent Plasticity based learning to occur at the associated synapses. Secondly, that bidirectional communication between neurons and astrocytes underpins dynamic coordination between neuron clusters. Although our composite AN model is presently applied to simplified neural structures and limited to coordination between localized neurons, the principle (which embodies structural, functional and dynamic complexity, and the modeling strategy may be extended to coordination among remote neuron clusters.

  11. Variation in regulator of G-protein signaling 17 gene (RGS17 is associated with multiple substance dependence diagnoses

    Directory of Open Access Journals (Sweden)

    Zhang Huiping

    2012-05-01

    Full Text Available Abstract Background RGS17 and RGS20 encode two members of the regulator of G-protein signaling RGS-Rz subfamily. Variation in these genes may alter their transcription and thereby influence the function of G protein-coupled receptors, including opioid receptors, and modify risk for substance dependence. Methods The association of 13 RGS17 and eight RGS20 tag single nucleotide polymorphisms (SNPs was examined with four substance dependence diagnoses (alcohol (AD, cocaine (CD, opioid (OD or marijuana (MjD] in 1,905 African Americans (AAs: 1,562 cases and 343 controls and 1,332 European Americans (EAs: 981 cases and 351 controls. Analyses were performed using both χ2 tests and logistic regression analyses that covaried sex, age, and ancestry proportion. Correlation of genotypes and mRNA expression levels was assessed by linear regression analyses. Results Seven RGS17 SNPs showed a significant association with at least one of the four dependence traits after a permutation-based correction for multiple testing (0.003≤Pempirical≤0.037. The G allele of SNP rs596359, in the RGS17 promoter region, was associated with AD, CD, OD, or MjD in both populations (0.005≤Pempirical≤0.019. This allele was also associated with significantly lower mRNA expression levels of RGS17 in YRI subjects (P = 0.002 and non-significantly lower mRNA expression levels of RGS17 in CEU subjects (P = 0.185. No RGS20 SNPs were associated with any of the four dependence traits in either population. Conclusions This study demonstrated that variation in RGS17 was associated with risk for substance dependence diagnoses in both AA and EA populations.

  12. Regulation of sclerostin expression in multiple myeloma by Dkk-1; a potential therapeutic strategy for myeloma bone disease

    Science.gov (United States)

    Eda, Homare; Santo, Loredana; Wein, Marc N.; Hu, Dorothy Z.; Cirstea, Diana D.; Nemani, Neeharika; Tai, Yu-Tzu; Raines, Sarah E.; Kuhstoss, Stuart Allen; Munshi, Nikhil C.; Kronenberg, Henry M.; Raje, Noopur S.

    2016-01-01

    Sclerostin is a potent inhibitor of osteoblastogenesis. Interestingly, newly diagnosed multiple myeloma (MM) patients have high levels of circulating sclerostin that correlate with disease stage and fractures. However, the source and impact of sclerostin in MM remains to be defined. Our goal was to determine the role of sclerostin in the biology of MM and its bone microenvironment as well as investigate the effect of targeting sclerostin with a neutralizing antibody (scl-Ab) in MM bone disease. Here we confirm increased sclerostin levels in MM compared to precursor disease states like Monoclonal Gammopathy of Undetermined Significance (MGUS) and smoldering MM. Furthermore, we found that a humanized MM xenograft mouse model bearing human MM cells (NOD-SCID.CB17 male mice injected intravenously with 2.5 million of MM1.S-Luc-GFP cells) demonstrated significantly higher concentrations of mouse-derived sclerostin, suggesting a microenvironmental source of sclerostin. Associated with the increased sclerostin levels, activated β-catenin expression levels were lower than normal in MM mouse bone marrow. Importantly, a high affinity grade scl-Ab reversed osteolytic bone disease in this animal model. Because scl-Ab did not demonstrate significant in vitro anti-MM activity, we combined it with the proteasome inhibitor, carfilzomib. Our data demonstrated that this combination therapy significantly inhibited tumor burden and improved bone disease in our in vivo MM mouse model. In agreement with our in vivo data, sclerostin expression was noted in marrow stromal cells and osteoblasts of MM patient BM samples. Moreover, MM cells stimulated sclerostin expression in immature osteoblasts while inhibiting osteoblast differentiation in vitro. This was in part regulated by Dkk-1 secreted by MM cells and is a potential mechanism contributing to the osteoblast dysfunction noted in MM. Our data confirms the role of sclerostin as a potential therapeutic target in MM bone disease, and

  13. FoxO1 regulates multiple metabolic pathways in the liver: effects on gluconeogenic, glycolytic, and lipogenic gene expression.

    Science.gov (United States)

    Zhang, Wenwei; Patil, Sandip; Chauhan, Balwant; Guo, Shaodong; Powell, David R; Le, Jamie; Klotsas, Angelos; Matika, Ryan; Xiao, Xiangshan; Franks, Roberta; Heidenreich, Kim A; Sajan, Mini P; Farese, Robert V; Stolz, Donna Beer; Tso, Patrick; Koo, Seung-Hoi; Montminy, Marc; Unterman, Terry G

    2006-04-14

    FoxO transcription factors are important targets of insulin action. To better understand the role of FoxO proteins in the liver, we created transgenic mice expressing constitutively active FoxO1 in the liver using the alpha1-antitrypsin promoter. Fasting glucose levels are increased, and glucose tolerance is impaired in transgenic (TGN) versus wild type (WT) mice. Interestingly, fasting triglyceride and cholesterol levels are reduced despite hyperinsulinemia, and post-prandial changes in triglyceride levels are markedly suppressed in TGN versus WT mice. Activation of pro-lipogenic signaling pathways (atypical protein kinase C and protein kinase B) and the ability to suppress beta-hydroxybutyrate levels are not impaired in TGN. In contrast, de novo lipogenesis measured with (3)H(2)O is suppressed by approximately 70% in the liver of TGN versus WT mice after refeeding. Gene-array studies reveal that the expression of genes involved in gluconeogenesis, glycerol transport, and amino acid catabolism is increased, whereas genes involved in glucose utilization by glycolysis, the pentose phosphate shunt, lipogenesis, and sterol synthesis pathways are suppressed in TGN versus WT. Studies with adenoviral vectors in isolated hepatocytes confirm that FoxO1 stimulates expression of gluconeogenic genes and suppresses expression of genes involved in glycolysis, the shunt pathway, and lipogenesis, including glucokinase and SREBP-1c. Together, these results indicate that FoxO proteins promote hepatic glucose production through multiple mechanisms and contribute to the regulation of other metabolic pathways important in the adaptation to fasting and feeding in the liver, including glycolysis, the pentose phosphate shunt, and lipogenic and sterol synthetic pathways.

  14. Folic Acid Is Able to Polarize the Inflammatory Response in LPS Activated Microglia by Regulating Multiple Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Antonia Cianciulli

    2016-01-01

    Full Text Available We investigated the ability of folic acid to modulate the inflammatory responses of LPS activated BV-2 microglia cells and the signal transduction pathways involved. To this aim, the BV-2 cell line was exposed to LPS as a proinflammatory response inducer, in presence or absence of various concentrations of folic acid. The production of nitric oxide (NO was determined by the Griess test. The levels of tumor necrosis factor-alpha (TNF-α, interleukin-1 beta (IL-1β, and IL-10 were determined by ELISA. Inducible NO synthase (iNOS, nuclear transcription factor-kappa B (NF-κB p65, MAPKs protein, and suppressors of cytokine signaling (SOCS1 and SOCS3 were analyzed by western blotting. TNF-α and IL-1β, as well as iNOS dependent NO production, resulted significantly inhibited by folic acid pretreatment in LPS-activated BV-2 cells. We also observed that folic acid dose-dependently upregulated both SOCS1 and SOCS3 expression in BV-2 cells, leading to an increased expression of the anti-inflammatory cytokine IL-10. Finally, p-IκBα, which indirectly reflects NF-κB complex activation, and JNK phosphorylation resulted dose-dependently downregulated by folic acid pretreatment of LPS-activated cells, whereas p38 MAPK phosphorylation resulted significantly upregulated by folic acid treatment. Overall, these results demonstrated that folic acid was able to modulate the inflammatory response in microglia cells, shifting proinflammatory versus anti-inflammatory responses through regulating multiple signaling pathways.

  15. Rationale and design of the Feeding Dynamic Intervention (FDI) study for self-regulation of energy intake in preschoolers.

    Science.gov (United States)

    Eneli, Ihuoma U; Tylka, Tracy L; Hummel, Jessica; Watowicz, Rosanna P; Perez, Susana A; Kaciroti, Niko; Lumeng, Julie C

    2015-03-01

    In 2011, the Institute of Medicine Early Childhood Prevention Policies Report identified feeding dynamics as an important focus area for childhood obesity prevention and treatment. Feeding dynamics includes two central components: (1) caregiver feeding practices (i.e., determining how, when, where, and what they feed their children) and (2) child eating behaviors (i.e., determining how much and what to eat from what food caregivers have provided). Although there has been great interest in overweight and obesity prevention and treatment in young children, they have not focused comprehensively on feeding dynamics. Interventions on feeding dynamics that reduce caregivers' excessive controlling and restrictive feeding practices and encourage the development of children's self-regulation of energy intake may hold promise for tackling childhood obesity especially in the young child but currently lack an evidence base. This manuscript describes the rationale and design for a randomized controlled trial designed to compare a group of mothers and their 3-to 5-year old children who received an intervention focused primarily on feeding dynamics called the Feeding Dynamic Intervention (FDI) with a Wait-list Control Group (WLC). The primary aim of the study will be to investigate the efficacy of the FDI for decreasing Eating in the Absence of Hunger (EAH) and improving energy compensation (COMPX). The secondary aim will be to examine the effect of the FDI in comparison to the WLC on maternal self-reported feeding practices and child satiety responsiveness. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Seasonal dynamics of insecticide resistance, multiple resistance, and morphometric variation in field populations of Culex pipiens.

    Science.gov (United States)

    Taskin, Belgin Gocmen; Dogaroglu, Taylan; Kilic, Sercan; Dogac, Ersin; Taskin, Vatan

    2016-05-01

    three different seasons. The results of this study have advanced our knowledge of the potential dynamics of insecticide resistance among populations of the Cx. pipiens complex. The implications of these results to the understanding of the evolution of insecticide resistance and the management of resistance in mosquitoes are discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. VLN2 Regulates Plant Architecture by Affecting Microfilament Dynamics and Polar Auxin Transport in Rice[OPEN

    Science.gov (United States)

    Wu, Shengyang; Xie, Yurong; Guo, Xiuping; Sheng, Peike; Wang, Juan; Wu, Chuanyin; Wang, Haiyang; Wan, Jianmin

    2015-01-01

    As a fundamental and dynamic cytoskeleton network, microfilaments (MFs) are regulated by diverse actin binding proteins (ABPs). Villins are one type of ABPs belonging to the villin/gelsolin superfamily, and their function is poorly understood in monocotyledonous plants. Here, we report the isolation and characterization of a rice (Oryza sativa) mutant defective in VILLIN2 (VLN2), which exhibits malformed organs, including twisted roots and shoots at the seedling stage. Cellular examination revealed that the twisted phenotype of the vln2 mutant is mainly caused by asymmetrical expansion of cells on the opposite sides of an organ. VLN2 is preferentially expressed in growing tissues, consistent with a role in regulating cell expansion in developing organs. Biochemically, VLN2 exhibits conserved actin filament bundling, severing and capping activities in vitro, with bundling and stabilizing activity being confirmed in vivo. In line with these findings, the vln2 mutant plants exhibit a more dynamic actin cytoskeleton network than the wild type. We show that vln2 mutant plants exhibit a hypersensitive gravitropic response, faster recycling of PIN2 (an auxin efflux carrier), and altered auxin distribution. Together, our results demonstrate that VLN2 plays an important role in regulating plant architecture by modulating MF dynamics, recycling of PIN2, and polar auxin transport. PMID:26486445

  18. Multiple sources driving the organic matter dynamics in two contrasting tropical mangroves

    International Nuclear Information System (INIS)

    Ray, R.; Shahraki, M.

    2016-01-01

    In this study, we have selected two different mangroves based on their geological, hydrological and climatological variations to investigate the origin (terrestrial, phytobenthos derived, and phytoplankton derived) of dissolved organic carbon (DOC), particulate organic carbon (POC) in the water column and the sedimentary OC using elemental ratios and stable isotopes. Qeshm Island, representing the Iranian mangroves received no attention before this study in terms of DOC, POC biogeochemistry and their sources unlike the Sundarbans (Indian side), the world's largest mangrove system. Slightly higher DOC concentrations in the Iranian mangroves were recorded in our field campaigns between 2011 and 2014, compared to the Sundarbans (315 ± 25 μM vs. 278 ± 42 μM), owing to the longer water residence times, while 9–10 times greater POC concentration (303 ± 37 μM, n = 82) was linked to both suspended load (345 ± 104 mg L − 1 ) and high algal production. Yearlong phytoplankton bloom in the mangrove-lined Persian Gulf was reported to be the perennial source of both POC and DOC contributing 80–86% to the DOC and 90–98% to the POC pool. Whereas in the Sundarbans, riverine input contributed 50–58% to the DOC pool and POC composition was regulated by the seasonal litter fall, river discharge and phytoplankton production. Algal derived organic matter (microphytobenthos) represented the maximum contribution (70–76%) to the sedimentary OC at Qeshm Island, while mangrove leaf litters dominated the OC pool in the Indian Sundarbans. Finally, hydrographical settings (i.e. riverine transport) appeared to be the determinant factor in differentiating OM sources in the water column between the dry and wet mangroves. - Highlights: • Sources of OC have been identified and compared between two contrasting mangroves. • Phytoplankton dominated the DOC and POC pool in the Iranian mangroves. • River input contributed half of the total DOC and part of POC in the Indian

  19. Multiple sources driving the organic matter dynamics in two contrasting tropical mangroves

    Energy Technology Data Exchange (ETDEWEB)

    Ray, R., E-mail: raghab.ray@gmail.com [Institut Universitaire Européen de la Mer, UBO, UMR 6539 LEMAR, rue Dumont dUrville, 29280 Plouzane (France); Leibniz Center for Tropical Marine Ecology, Fahrenheitstr. 6, 28359 Bremen (Germany); Shahraki, M. [Leibniz Center for Tropical Marine Ecology, Fahrenheitstr. 6, 28359 Bremen (Germany); Alfred Wegener Institute, Helmholtz Centre for Polar and Marine Research, Am Handelshafen 12, 27570 Bremerhaven (Germany)

    2016-11-15

    In this study, we have selected two different mangroves based on their geological, hydrological and climatological variations to investigate the origin (terrestrial, phytobenthos derived, and phytoplankton derived) of dissolved organic carbon (DOC), particulate organic carbon (POC) in the water column and the sedimentary OC using elemental ratios and stable isotopes. Qeshm Island, representing the Iranian mangroves received no attention before this study in terms of DOC, POC biogeochemistry and their sources unlike the Sundarbans (Indian side), the world's largest mangrove system. Slightly higher DOC concentrations in the Iranian mangroves were recorded in our field campaigns between 2011 and 2014, compared to the Sundarbans (315 ± 25 μM vs. 278 ± 42 μM), owing to the longer water residence times, while 9–10 times greater POC concentration (303 ± 37 μM, n = 82) was linked to both suspended load (345 ± 104 mg L{sup −} {sup 1}) and high algal production. Yearlong phytoplankton bloom in the mangrove-lined Persian Gulf was reported to be the perennial source of both POC and DOC contributing 80–86% to the DOC and 90–98% to the POC pool. Whereas in the Sundarbans, riverine input contributed 50–58% to the DOC pool and POC composition was regulated by the seasonal litter fall, river discharge and phytoplankton production. Algal derived organic matter (microphytobenthos) represented the maximum contribution (70–76%) to the sedimentary OC at Qeshm Island, while mangrove leaf litters dominated the OC pool in the Indian Sundarbans. Finally, hydrographical settings (i.e. riverine transport) appeared to be the determinant factor in differentiating OM sources in the water column between the dry and wet mangroves. - Highlights: • Sources of OC have been identified and compared between two contrasting mangroves. • Phytoplankton dominated the DOC and POC pool in the Iranian mangroves. • River input contributed half of the total DOC and part of POC in

  20. The atypical Rho GTPase RhoD is a regulator of actin cytoskeleton dynamics and directed cell migration

    International Nuclear Information System (INIS)

    Blom, Magdalena; Reis, Katarina; Heldin, Johan; Kreuger, Johan; Aspenström, Pontus

    2017-01-01

    RhoD belongs to the Rho GTPases, a protein family responsible for the regulation and organization of the actin cytoskeleton, and, consequently, many cellular processes like cell migration, cell division and vesicle trafficking. Here, we demonstrate that the actin cytoskeleton is dynamically regulated by increased or decreased protein levels of RhoD. Ectopic expression of RhoD has previously been shown to give an intertwined weave of actin filaments. We show that this RhoD-dependent effect is detected in several cell types and results in a less dynamic actin filament system. In contrast, RhoD depletion leads to increased actin filament-containing structures, such as cortical actin, stress fibers and edge ruffles. Moreover, vital cellular functions such as cell migration and proliferation are defective when RhoD is silenced. Taken together, we present data suggesting that RhoD is an important component in the control of actin dynamics and directed cell migration. - Highlights: • Increased RhoD expression leads to loss of actin structures, e.g. stress fibers and gives rise to decreased actin dynamics. • RhoD knockdown induces various actin-containing structures such as edge ruffles, stress fibers and cortical actin, in a cell-type specific manner. • RhoD induces specific actin rearrangements depending on its subcellular localization. • RhoD knockdown has effects on cellular processes, such as directed cell migration and proliferation.

  1. The atypical Rho GTPase RhoD is a regulator of actin cytoskeleton dynamics and directed cell migration

    Energy Technology Data Exchange (ETDEWEB)

    Blom, Magdalena; Reis, Katarina [Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm (Sweden); Heldin, Johan [Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala SE-751 22 Uppsala (Sweden); Kreuger, Johan [Department of Medical Cell Biology, Science for Life Laboratory, Uppsala University, SE-751 23 Uppsala (Sweden); Aspenström, Pontus, E-mail: pontus.aspenstrom@ki.se [Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm (Sweden)

    2017-03-15

    RhoD belongs to the Rho GTPases, a protein family responsible for the regulation and organization of the actin cytoskeleton, and, consequently, many cellular processes like cell migration, cell division and vesicle trafficking. Here, we demonstrate that the actin cytoskeleton is dynamically regulated by increased or decreased protein levels of RhoD. Ectopic expression of RhoD has previously been shown to give an intertwined weave of actin filaments. We show that this RhoD-dependent effect is detected in several cell types and results in a less dynamic actin filament system. In contrast, RhoD depletion leads to increased actin filament-containing structures, such as cortical actin, stress fibers and edge ruffles. Moreover, vital cellular functions such as cell migration and proliferation are defective when RhoD is silenced. Taken together, we present data suggesting that RhoD is an important component in the control of actin dynamics and directed cell migration. - Highlights: • Increased RhoD expression leads to loss of actin structures, e.g. stress fibers and gives rise to decreased actin dynamics. • RhoD knockdown induces various actin-containing structures such as edge ruffles, stress fibers and cortical actin, in a cell-type specific manner. • RhoD induces specific actin rearrangements depending on its subcellular localization. • RhoD knockdown has effects on cellular processes, such as directed cell migration and proliferation.

  2. Dynamics and regulation of glycolysis-tricarboxylic acid metabolism in the midgut of Spodoptera litura during metamorphosis.

    Science.gov (United States)

    Hu, D; Luo, W; Fan, L F; Liu, F L; Gu, J; Deng, H M; Zhang, C; Huang, L H; Feng, Q L

    2016-04-01

    Significant changes usually take place in the internal metabolism of insects during metamorphosis. The glycolysis-tricarboxylic acid (glycolysis-TCA) pathway is important for energy metabolism. To elucidate its dynamics, the mRNA levels of genes involved in this pathway were examined in the midgut of Spodoptera litura during metamorphosis, and the pyruvate content was quantified. The expression patterns of these genes in response to starvation were examined, and the interaction between protein phosphatase 1 (PP1) and phosphofructokinase (PFK) was studied. The results revealed that the expression or activities of most glycolytic enzymes was down-regulated in prepupae and then recovered in some degree in pupae, and all TCA-related genes were remarkably suppressed in both the prepupae and pupae. Pyruvate was enriched in the pupal midgut. Taken together, these results suggest that insects decrease both glycolysis and TCA in prepupae to save energy and then up-regulate glycolysis but down-regulate TCA in pupae to increase the supply of intermediates for construction of new organs. The expression of all these genes were down-regulated by starvation, indicating that non-feeding during metamorphosis may be a regulator of glycolysis-TCA pathway in the midgut. Importantly, interaction between PP1 and PFK was identified and is suggested to be involved in the regulation of glycolysis. © 2015 The Royal Entomological Society.

  3. Exploring pre-channelization bar and planform dynamics of a large regulated Alpine River

    Science.gov (United States)

    Zen, Simone; Zolezzi, Guido; Scorpio, Vittoria; Mastronunzio, Marco; Bertoldi, Walter; Comiti, Francesco; Daiprà, Elena

    2017-04-01

    As a consequence of heavy channelization mostly carried out in the 1800s, the planform and bars morphodynamics of many large European rivers is hardly detectable even from aerial images dating back several decades, because of the marked reduction of the channel width and of the related morphological complexity. However, when available, historical maps can provide quantitative information on the morphology that characterized these rivers before massive human intervention occurred. In this work we focus on a 100 km reach of the Adige - Etsch River, NE, Italy, with the aim of exploring the short-term (some decades) morphological dynamics that might have characterized the pre-channelized river bed and planform in its single-thread reaches before heavy human intervention. To this aim we integrate the application of a morphodynamic analytical model for meandering rivers with irregularly varying curvature and channel width with the multi-temporal analysis of pre-channelization historical maps. The work focuses on the sinuous and meandering reaches once characterized by spatially varying channel width, and presence of alternate, point and mid-channel bars. Challenges in such kind of integrated analysis are posed by the reconstruction of channel - forming streamflow values and of sediment size that may have characterized the river reaches up to nearly three centuries ago prior to heavy regulation. Formative discharge ranges have been obtained as those generating the best geometrical fit between the modeled river bed morphology and the one observed from the maps. Once calibrated by this procedure, the model was fed through the estimated discharge value to compute the longitudinal variability of the outer-bank shear stress, as a proxy for the locations potentially affected by fluvial bank erosion. The historical maps reveal that during the 17th and 18th century, before the massive channelization, the river morphodynamics was already far from being "natural", especially

  4. Transcriptional regulation is a major controller of cell cycle transition dynamics

    DEFF Research Database (Denmark)

    Romanel, Alessandro; Jensen, Lars Juhl; Cardelli, Luca

    2012-01-01

    DNA replication, mitosis and mitotic exit are critical transitions of the cell cycle which normally occur only once per cycle. A universal control mechanism was proposed for the regulation of mitotic entry in which Cdk helps its own activation through two positive feedback loops. Recent discoveries...... in various organisms showed the importance of positive feedbacks in other transitions as well. Here we investigate if a universal control system with transcriptional regulation(s) and post-translational positive feedback(s) can be proposed for the regulation of all cell cycle transitions. Through...

  5. Dynamics of study strategies and teacher regulation in virtual patient learning activities: a cross sectional survey.

    Science.gov (United States)

    Edelbring, Samuel; Wahlström, Rolf

    2016-04-23

    Students' self-regulated learning becomes essential with increased use of exploratory web-based activities such as virtual patients (VPs). The purpose was to investigate the interplay between students' self-regulated learning strategies and perceived benefit in VP learning activities. A cross-sectional study (n = 150) comparing students' study strategies and perceived benefit of a virtual patient learning activity in a clinical clerkship preparatory course. Teacher regulation varied among three settings and was classified from shared to strong. These settings were compared regarding their respective relations between regulation strategies and perceived benefit of the virtual patient activity. Self-regulation learning strategy was generally associated with perceived benefit of the VP activities (rho 0.27, p regulated settings. The external regulation strategy did generally associate weakly with perceived benefit (rho 0.17, p regulation seem to be productive for increasing learners' perceived benefit. Awareness of the interplay among teacher regulation (external) and various study strategies can increase the value of flexible web-based learning resources to students.

  6. G1-phase regulators, cyclin D1, cyclin D2, and cyclin D3: up-regulation at gastrulation and dynamic expression during neurulation.

    Science.gov (United States)

    Wianny, F; Real, F X; Mummery, C L; Van Rooijen, M; Lahti, J; Samarut, J; Savatier, P

    1998-05-01

    Gastrulation in rodents is associated with an increase in the rate of growth and with the start of differentiation within the embryo proper. In an effort to understand the role played by the cell cycle control in these processes, expression of cyclin D1, D2, and D3--three major positive regulators of the G1/S transition--has been investigated by in situ hybrization and RT-PCR. Cyclin D1 and D2 transcripts are first detected in the epiblast at gastrulation, when a proliferative burst occurs, and subsequently in its differentiated derivatives within the embryo proper, indicating that activation of their expression takes place prior to the differentiation of epiblast progenitors. In contrast, cyclin D3 transcript is undetectable in the epiblast itself and its expression is activated exclusively in extraembryonic tissues of both epiblast and trophoblast origin. During neurulation, expression of each cyclin D RNA is dynamically regulated along the anterior-posterior axis. In the hindbrain, cyclin D1 and D2 show distinct segment-specific restricted expression and this pattern is conserved between mouse and chick. These results strongly suggest that D-type cyclins act as developmental regulators.

  7. CDK and MAPK Synergistically Regulate Signaling Dynamics via a Shared Multi-site Phosphorylation Region on the Scaffold Protein Ste5.

    Science.gov (United States)

    Repetto, María Victoria; Winters, Matthew J; Bush, Alan; Reiter, Wolfgang; Hollenstein, David Maria; Ammerer, Gustav; Pryciak, Peter M; Colman-Lerner, Alejandro

    2018-03-15

    We report an unanticipated system of joint regulation by cyclin-dependent kinase (CDK) and mitogen-activated protein kinase (MAPK), involving collaborative multi-site phosphorylation of a single substrate. In budding yeast, the protein Ste5 controls signaling through a G1 arrest pathway. Upon cell-cycle entry, CDK inhibits Ste5 via multiple phosphorylation sites, disrupting its membrane association. Using quantitative time-lapse microscopy, we examined Ste5 membrane recruitment dynamics at different cell-cycle stages. Surprisingly, in S phase, where Ste5 recruitment should be blocked, we observed an initial recruitment followed by a steep drop-off. This delayed inhibition revealed a requirement for both CDK activity and negative feedback from the pathway MAPK Fus3. Mutagenesis, mass spectrometry, and electrophoretic analyses suggest that the CDK and MAPK modify shared sites, which are most extensively phosphorylated when both kinases are active and able to bind their docking sites on Ste5. Such collaborative phosphorylation can broaden regulatory inputs and diversify output dynamics of signaling pathways. Copyright © 2018 Elsevier Inc. All rights reserved.

  8. Influence of growth regulators and physical state of the culture medium on the in vitro multiplication of Colocasia esculenta clone 'INIVIT MC2001'

    Directory of Open Access Journals (Sweden)

    Diosdada Galvez Guerra

    2013-10-01

    Full Text Available To achieve adequate results in the in vitro multiplication of taro cultivars is required to standardize the culture conditions. The aim of this study was to determine the influence of growth regulators and physical state of the culture medium on in vitro multiplication of Colocasia esculenta clone `INIVITC2001'. Five treatments involving indole acetic acid (IAA and 6-benzylaminopurine (6-BAP were established: 1.0 mg l-1 IAA + 3.0 mg l-1 6-BAP, 3.0 mg l-1 6-BAP, 4.0 mg l-1 6-BAP, 5.0 mg l-1 6-BAP, 1.0 mg l-1 IAA + 6.0 mg l-1 6-BAP. After 30 days of culture the multiplication coefficient was calculated. Furthermore, the effect on the physical state of the culture medium on this variable during three subcultures was determined. When the culture medium consisting of MS salts and vitamins with 4.0 mg l-1 of 6-BAP was used the greater multiplication coefficient was obtained. Handling the physical state of the culture medium for three subcultures influenced the multiplication coefficient in each subculture, in average coefficient multiplication of three subcultures and the total number of explants obtained after three subcultures. With the culture medium in semisolid state better growth and higher explants multiplication coefficient was achieved. Key words: AIA, 6-BAP, taro, semisolid medium

  9. A cassette of basic amino acids in histone H2B regulates nucleosome dynamics and access to DNA damage.

    Science.gov (United States)

    Rodriguez, Yesenia; Duan, Mingrui; Wyrick, John J; Smerdon, Michael J

    2018-03-27

    Nucleosome dynamics, such as spontaneous DNA unwrapping, are postulated to have a critical role in regulating the access of DNA repair machinery to DNA lesions within nucleosomes. However, the specific histone domains that regulate nucleosome dynamics and their impact on DNA repair are not well understood. Previous studies have identified the histone H2B repression (or HBR) domain, a highly conserved, basic region in the N-terminal tail of histone H2B, which significantly influences gene expression, chromatin assembly, and DNA damage and repair. However, knowledge about the molecular mechanism(s) that may account for these observations is limited. Here, we characterized the stability and dynamics of ΔHBR mutant nucleosome core particles (NCPs) in vitro by restriction-enzyme accessibility, FRET, and temperature-induced sliding of histone octamers. Our results indicate that ΔHBR NCPs are more dynamic and the steady-state fraction of the ΔHBR NCP population occupying the unwrapped state is larger than that of WT NCPs. Moreover, ΔHBR-histone octamers are more susceptible to temperature-induced sliding on DNA than WT histone octamers. Notably, the activity of base-excision repair (BER) enzymes at uracil lesions and single-nucleotide gaps is enhanced in a site-specific manner in ΔHBR NCPs and correlates well with increased DNA unwrapping in these damaged regions. Finally, removal of the HBR domain is insufficient for completely alleviating the structural constraints imposed by histone octamers on the activity of BER enzymes. In summary, our findings indicate that the conserved HBR domain of histone H2B regulates the accessibility of repair factors to DNA lesions in nucleosomes. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

  10. QSSPN: dynamic simulation of molecular interaction networks describing gene regulation, signalling and whole-cell metabolism in human cells.

    Science.gov (United States)

    Fisher, Ciarán P; Plant, Nicholas J; Moore, J Bernadette; Kierzek, Andrzej M

    2013-12-15

    Dynamic simulation of genome-scale molecular interaction networks will enable the mechanistic prediction of genotype-phenotype relationships. Despite advances in quantitative biology, full parameterization of whole-cell models is not yet possible. Simulation methods capable of using available qualitative data are required to develop dynamic whole-cell models through an iterative process of modelling and experimental validation. We formulate quasi-steady state Petri nets (QSSPN), a novel method integrating Petri nets and constraint-based analysis to predict the feasibility of qualitative dynamic behaviours in qualitative models of gene regulation, signalling and whole-cell metabolism. We present the first dynamic simulations including regulatory mechanisms and a genome-scale metabolic network in human cell, using bile acid homeostasis in human hepatocytes as a case study. QSSPN simulations reproduce experimentally determined qualitative dynamic behaviours and permit mechanistic analysis of genotype-phenotype relationships. The model and simulation software implemented in C++ are available in supplementary material and at http://sysbio3.fhms.surrey.ac.uk/qsspn/.

  11. Regulation-Structured Dynamic Metabolic Model Provides a Potential Mechanism for Delayed Enzyme Response in Denitrification Process

    Energy Technology Data Exchange (ETDEWEB)

    Song, Hyun-Seob; Thomas, Dennis G.; Stegen, James C.; Li, Minjing; Liu, Chongxuan; Song, Xuehang; Chen, Xingyuan; Fredrickson, Jim K.; Zachara, John M.; Scheibe, Timothy D.

    2017-09-29

    In a recent study of denitrification dynamics in hyporheic zone sediments, we observed a significant time lag (up to several days) in enzymatic response to the changes in substrate concentration. To explore an underlying mechanism and understand the interactive dynamics between enzymes and nutrients, we developed a trait-based model that associates a community’s traits with functional enzymes, instead of typically used species guilds (or functional guilds). This enzyme-based formulation allows to collectively describe biogeochemical functions of microbial communities without directly parameterizing the dynamics of species guilds, therefore being scalable to complex communities. As a key component of modeling, we accounted for microbial regulation occurring through transcriptional and translational processes, the dynamics of which was parameterized based on the temporal profiles of enzyme concentrations measured using a new signature peptide-based method. The simulation results using the resulting model showed several days of a time lag in enzymatic responses as observed in experiments. Further, the model showed that the delayed enzymatic reactions could be primarily controlled by transcriptional responses and that the dynamics of transcripts and enzymes are closely correlated. The developed model can serve as a useful tool for predicting biogeochemical processes in natural environments, either independently or through integration with hydrologic flow simulators.

  12. The Armc10/SVH gene: genome context, regulation of mitochondrial dynamics and protection against Aβ-induced mitochondrial fragmentation.

    Science.gov (United States)

    Serrat, R; Mirra, S; Figueiro-Silva, J; Navas-Pérez, E; Quevedo, M; López-Doménech, G; Podlesniy, P; Ulloa, F; Garcia-Fernàndez, J; Trullas, R; Soriano, E

    2014-04-10

    Mitochondrial function and dynamics are essential for neurotransmission, neural function and neuronal viability. Recently, we showed that the eutherian-specific Armcx gene cluster (Armcx1-6 genes), located in the X chromosome, encodes for a new family of proteins that localise to mitochondria, regulating mitochondrial trafficking. The Armcx gene cluster evolved by retrotransposition of the Armc10 gene mRNA, which is present in all vertebrates and is considered to be the ancestor gene. Here we investigate the genomic organisation, mitochondrial functions and putative neuroprotective role of the Armc10 ancestor gene. The genomic context of the Armc10 locus shows considerable syntenic conservation among vertebrates, and sequence comparisons and CHIP-data suggest the presence of at least three conserved enhancers. We also show that the Armc10 protein localises to mitochondria and that it is highly expressed in the brain. Furthermore, we show that Armc10 levels regulate mitochondrial trafficking in neurons, but not mitochondrial aggregation, by controlling the number of moving mitochondria. We further demonstrate that the Armc10 protein interacts with the KIF5/Miro1-2/Trak2 trafficking complex. Finally, we show that overexpression of Armc10 in neurons prevents Aβ-induced mitochondrial fission and neuronal death. Our data suggest both conserved and differential roles of the Armc10/Armcx gene family in regulating mitochondrial dynamics in neurons, and underscore a protective effect of the Armc10 gene against Aβ-induced toxicity. Overall, our findings support a further degree of regulation of mitochondrial dynamics in the brain of more evolved mammals.

  13. Multiple-level regulation of 2,4-diacetylphloroglucinol production by the sigma regulator PsrA in Pseudomonas fluorescens 2P24.

    Directory of Open Access Journals (Sweden)

    Xiaogang Wu

    Full Text Available BACKGROUND: Pseudomonas fluorescens 2P24 is a rhizospheric bacterium that aggressively colonizes the plant roots. It produces the antibiotic 2,4-diacetylphoroglucinol (2,4-DAPG, which contributes to the protection of various crop plants against soil borne diseases caused by bacterial and fungal pathogens. The biosynthesis of 2,4-DAPG is regulated at the transcriptional level in the expression of the phlACBD operon as well as at the posttranscriptional level by the Gac/Rsm signal transduction pathway. However, the detailed mechanism of such regulation is not clear. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we identified a binding site for the sigma regulator PsrA in the promoter region of the phlA gene. Electrophoretic mobility shift experiments revealed direct and specific binding of PsrA to the phlA promoter region. Consistent with the fact that its binding site locates within the promoter region of phlA, PsrA negatively regulates phlA expression, and its inactivation led to significant increase in 2,4-DAPG production. Interestingly, PsrA also activates the expression of the sigma factor RpoS, which negatively regulates 2,4-DAPG production by inducing the expression of the RNA-binding protein RsmA. CONCLUSIONS/SIGNIFICANCE: These results suggest that PsrA is an important regulator that modulates 2,4-DAPG biosynthesis at both transcriptional and posttranscriptional levels.

  14. Regulating Multiple Variables To Understand the Nucleation and Growth and Transformation of PbS Nanocrystal Superlattices.

    Science.gov (United States)

    Wang, Zhongwu; Bian, Kaifu; Nagaoka, Yasutaka; Fan, Hongyou; Cao, Y Charles

    2017-10-18

    Nanocrystals (NCs) can self-assemble into ordered superlattices with collective properties, but the ability for controlling NC assembly remains poorly understandable toward achievement of desired superlattice. This work regulates several key variables of PbS NC assembly (e.g., NC concentration and solubility, solvent type, evaporation rate, seed mediation and thermal treatment), and thoroughly exploits the nucleation and growth as well as subsequent superlattice transformation of NC assembles and underneath mechanisms. PbS NCs in toluene self-assemble into a single face-centered-cubic (fcc) and body-centered-cubic (bcc) superlattice, respectively, at concentrations ≤17.5 and ≥70 mg/mL, but an intermediate concentration between them causes the coexistence of the two superlattices. Differently, NCs in hexane or chloroform self-assemble into only a single bcc superlattice. Distinct controls of NC assembly in solvent with variable concentrations confirm the NC concentration/solubility mediated nucleation and growth of superlattice, in which an evaporation-induced local gradient of NC concentration causes simultaneous nucleation of the two superlattices. The observation for the dense packing planes of NCs in fast growing fcc rather than bcc reveals the difference of entropic driving forces responsible for the two distinct superlattices. Decelerating the solvent evaporation does not amend the superlattice symmetry, but improves the superlattice crystallinity. In addition to shrinking the superlattice volume, thermal treatment also transforms the bcc to an fcc superlattice at 175 °C. Through a seed-meditated growth, the concentration-dependent superlattice does not change lattice symmetry over the course of continuous growth, whereas the newly nucleated secondary small nuclei through a concentration change have relatively higher surface energy and quickly dissolve in solution, providing additional NC sources for the ripening of the primarily nucleated larger and

  15. Regulation of Sclerostin Expression in Multiple Myeloma by Dkk-1: A Potential Therapeutic Strategy for Myeloma Bone Disease.

    Science.gov (United States)

    Eda, Homare; Santo, Loredana; Wein, Marc N; Hu, Dorothy Z; Cirstea, Diana D; Nemani, Neeharika; Tai, Yu-Tzu; Raines, Sarah E; Kuhstoss, Stuart Allen; Munshi, Nikhil C; Kronenberg, Henry M; Raje, Noopur S

    2016-06-01

    Sclerostin is a potent inhibitor of osteoblastogenesis. Interestingly, newly diagnosed multiple myeloma (MM) patients have high levels of circulating sclerostin that correlate with disease stage and fractures. However, the source and impact of sclerostin in MM remains to be defined. Our goal was to determine the role of sclerostin in the biology of MM and its bone microenvironment as well as investigate the effect of targeting sclerostin with a neutralizing antibody (scl-Ab) in MM bone disease. Here we confirm increased sclerostin levels in MM compared with precursor disease states like monoclonal gammopathy of undetermined significance (MGUS) and smoldering MM. Furthermore, we found that a humanized MM xenograft mouse model bearing human MM cells (NOD-SCID.CB17 male mice injected intravenously with 2.5 million of MM1.S-Luc-GFP cells) demonstrated significantly higher concentrations of mouse-derived sclerostin, suggesting a microenvironmental source of sclerostin. Associated with the increased sclerostin levels, activated β-catenin expression levels were lower than normal in MM mouse bone marrow. Importantly, a high-affinity grade scl-Ab reversed osteolytic bone disease in this animal model. Because scl-Ab did not demonstrate significant in vitro anti-MM activity, we combined it with the proteasome inhibitor carfilzomib. Our data demonstrated that this combination therapy significantly inhibited tumor burden and improved bone disease in our in vivo MM mouse model. In agreement with our in vivo data, sclerostin expression was noted in marrow stromal cells and osteoblasts of MM patient bone marrow samples. Moreover, MM cells stimulated sclerostin expression in immature osteoblasts while inhibiting osteoblast differentiation in vitro. This was in part regulated by Dkk-1 secreted by MM cells and is a potential mechanism contributing to the osteoblast dysfunction noted in MM. Our data confirm the role of sclerostin as a potential therapeutic target in MM bone disease

  16. Impact of multiple quaternary ammonium salts on dynamic properties of BSA adsorption layer at different pH values.

    Science.gov (United States)

    Mei, Qi-Xiang; Lai, Lu; Zhou, Zhi-Qiang; Mei, Ping; Ren, Zhao-Hua; Zheng, Yan-Cheng; Liu, Yi

    2017-10-18

    The interaction mechanism of multiple quaternary ammonium salts (MQAS) with bovine serum albumin (BSA) was examined by the fluorescence quenching method and circular dichroism (CD) spectra. Moreover, the effects of MQAS on the dynamic properties of BSA adsorption layers at different pH values were investigated using dilational interfacial rheology. Results show that the quenching constants increase with an increase in pH values and decrease with an increase in the experiment temperature at pH 5.3. The quenching mechanism is static quenching, and the electrostatic force dominates the interaction between MQAS and BSA at pH 5.3. Due to three positive head groups, MQAS can significantly affect the dynamic interfacial activity of BSA molecules at a relatively low concentration. At pH 4.3, the electrostatic repulsion is unfavorable for the formation of MQAS/BSA complexes. Consequently, MQAS molecules will replace BSA molecules from the interface by competitive adsorption. At the pH value above the isoelectric point of BSA, the electrostatic attraction is better for the formation of MQAS/BSA complexes, which exhibit a rapid adsorption rate and an enhanced interfacial activity. Moreover, the kinetic dependencies of interfacial dilational elasticity for the MQAS/BSA mixtures become nonmonotonous. The appearance of the maximum interfacial elasticity values can be attributed to the formation of tails and loops, which suggests that the addition of MQAS destroys the secondary and tertiary structure of protein in the bulk phase. In addition, the effects of MQAS on the secondary structure of protein were demonstrated by CD spectra.

  17. Steam drum level dynamics in a multiple loop natural circulation system of a pressure-tube type boiling water reactor

    International Nuclear Information System (INIS)

    Jain, Vikas; Kulkarni, P.P.; Nayak, A.K.; Vijayan, P.K.; Saha, D.; Sinha, R.K.

    2011-01-01

    Highlights: → We have highlighted the problem of drum level dynamics in a multiple loop type NC system using RELAP5 code. → The need of interconnections in steam and liquid spaces close to drum is established. → The steam space interconnections equalize pressure and liquid space interconnections equalize level. → With this scheme, the system can withstand anomalous conditions. → However, the controller is found to be inevitable for inventory balance. - Abstract: Advanced Heavy Water Reactor (AHWR) is a pressure tube type boiling water reactor employing natural circulation as the mode of heat removal under all the operating conditions. Main heat transport system (MHTS) of AHWR is essentially a multi-loop natural circulation system with all the loops connected to each other. Each loop of MHTS has a steam drum that provides for gravity based steam-water separation. Steam drum level is a very critical parameter especially in multi-loop natural circulation systems as large departures from the set point may lead to ineffective separation of steam-water or may affect the driving head. However, such a system is susceptible to steam drum level anomalies under postulated asymmetrical operating conditions among the different quadrants of the core like feedwater flow distribution anomaly among the steam drums or power anomaly among the core quadrants. Analyses were carried out to probe such scenarios and unravel the underlying dynamics of steam drum level using system code RELAP5/Mod3.2. In addition, a scheme to obviate such problem in a passive manner without dependence on level controller was examined. It was concluded that steam drums need to be connected in the liquid as well as steam space to make the system tolerant to asymmetrical operating conditions.

  18. [Chaotic dynamic process of multiple organs dysfunction syndrome and the regulatory function of shenqin liquid on it].

    Science.gov (United States)

    Liang, Jun-Xiong; Weng, Shu-He; Chen, Jing-He

    2008-07-01

    To explore the chaotic dynamic process of multiple organs dysfunction syndrome (MODS) and the regulatory effect of Shenqin Liquid (SQL), a Chinese herbal liquid preparation with the action of purging and qi-tonifying. Eighty SD rats were divided into 4 groups, and were given suspension of zymosan A and paraffine (1 mL/kg) by peritoneal injection except for those in the blank control group to set up the multiple organs dysfunction syndrome (MODS) model. Low and high doses SQL were administered twice at the doses of 30 and 60 g/kg of SQL respectively at an interval of 8 h per day before modeling. Serum concentration of tumor necrosis factor alpha (TNF-alpha) and nitric oxide (NO) in MODS model animals were tested diachronically, eg. 12, 6 h before modeling, during modeling, 6 and 12 h after modeling, and then the mathematic models were built up with compartment analysis. Lyapunov exponents (LE) of the mathematic models were calculated to evaluate their chaotic characteristics of movement and the degree of chaos was ascertained with the correlation dimension (CD). The serum levels of TNF-alpha and NO were significantly higher than those in the bland control group at modeling, 6, and 12 h after modeling (P SQL were significantly lower than the model group (P SQL was significantly lower than that in the low dose group (P 0 respectively; in the low dose and high dose SQL treated groups, CD was 0.517 and 0.653 respectively and LE >0. CD of NO movement in the blank control group was 0.670 and with LE 0; in the low dose SQL group, 0.574 and in the high dose SQL group 0.850, and LE SQL can intervene the movement of TNF-alpha and NO, decrease the complexity of their chaotic movement, and make them return back to a stable state.

  19. Multi-Layer Identification of Highly-Potent ABCA1 Up-Regulators Targeting LXRβ Using Multiple QSAR Modeling, Structural Similarity Analysis, and Molecular Docking

    Directory of Open Access Journals (Sweden)

    Meimei Chen

    2016-11-01

    Full Text Available In this study, in silico approaches, including multiple QSAR modeling, structural similarity analysis, and molecular docking, were applied to develop QSAR classification models as a fast screening tool for identifying highly-potent ABCA1 up-regulators targeting LXRβ based on a series of new flavonoids. Initially, four modeling approaches, including linear discriminant analysis, support vector machine, radial basis function neural network, and classification and regression trees, were applied to construct different QSAR classification models. The statistics results indicated that these four kinds of QSAR models were powerful tools for screening highly potent ABCA1 up-regulators. Then, a consensus QSAR model was developed by combining the predictions from these four models. To discover new ABCA1 up-regulators at maximum accuracy, the compounds in the ZINC database that fulfilled the requirement of structural similarity of 0.7 compared to known potent ABCA1 up-regulator were subjected to the consensus QSAR model, which led to the discovery of 50 compounds. Finally, they were docked into the LXRβ binding site to understand their role in up-regulating ABCA1 expression. The excellent binding modes and docking scores of 10 hit compounds suggested they were highly-potent ABCA1 up-regulators targeting LXRβ. Overall, this study provided an effective strategy to discover highly potent ABCA1 up-regulators.

  20. Ab initio multiple spawning dynamics study of dimethylnitramine and dimethylnitramine-Fe complex to model their ultrafast nonadiabatic chemistry.

    Science.gov (United States)

    Bera, Anupam; Ghosh, Jayanta; Bhattacharya, Atanu

    2017-07-28

    Conical intersections are now firmly established to be the key features in the excited electronic state processes of polyatomic energetic molecules. In the present work, we have explored conical intersection-mediated nonadiabatic chemical dynamics of a simple analogue nitramine molecule, dimethylnitramine (DMNA, containing one N-NO 2 energetic group), and its complex with an iron atom (DMNA-Fe). For this task, we have used the ab initio multiple spawning (AIMS) dynamics simulation at the state averaged-complete active space self-consistent field(8,5)/6-31G(d) level of theory. We have found that DMNA relaxes back to the ground (S 0 ) state following electronic excitation to the S 1 excited state [which is an (n,π*) excited state] with a time constant of approximately 40 fs. This AIMS result is in very good agreement with the previous surface hopping-result and femtosecond laser spectroscopy result. DMNA does not dissociate during this fast internal conversion from the S 1 to the S 0 state. DMNA-Fe also undergoes extremely fast relaxation from the upper S 1 state to the S 0 state; however, this relaxation pathway is dissociative in nature. DMNA-Fe undergoes initial Fe-O, N-O, and N-N bond dissociations during relaxation from the upper S 1 state to the ground S 0 state through the respective conical intersection. The AIMS simulation reveals the branching ratio of these three channels as N-N:Fe-O:N-O = 6:3:1 (based on 100 independent simulations). Furthermore, the AIMS simulation reveals that the Fe-O bond dissociation channel exhibits the fastest (time constant 24 fs) relaxation, while the N-N bond dissociation pathway features the slowest (time constant 128 fs) relaxation. An intermediate time constant (30 fs) is found for the N-O bond dissociation channel. This is the first nonadiabatic chemical dynamics study of metal-contained energetic molecules through conical intersections.

  1. Dynamic regulation of metabolic flux in engineered bacteria using a pathway-independent quorum-sensing circuit.

    Science.gov (United States)

    Gupta, Apoorv; Reizman, Irene M Brockman; Reisch, Christopher R; Prather, Kristala L J

    2017-03-01

    Metabolic engineering of microorganisms to produce desirable products on an industrial scale can result in unbalanced cellular metabolic networks that reduce productivity and yield. Metabolic fluxes can be rebalanced using dynamic pathway regulation, but few broadly applicable tools are available to achieve this. We present a pathway-independent genetic control module that can be used to dynamically regulate the expression of target genes. We apply our module to identify the optimal point to redirect glycolytic flux into heterologous engineered pathways in Escherichia coli, resulting in titers of myo-inositol increased 5.5-fold and titers of glucaric acid increased from unmeasurable to >0.8 g/L, compared to the parent strains lacking dynamic flux control. Scaled-up production of these strains in benchtop bioreactors resulted in almost ten- and fivefold increases in specific titers of myo-inositol and glucaric acid, respectively. We also used our module to control flux into aromatic amino acid biosynthesis to increase titers of shikimate in E. coli from unmeasurable to >100 mg/L.

  2. An integrated mechanism of pediatric pseudotumor cerebri syndrome: evidence of bioenergetic and hormonal regulation of cerebrospinal fluid dynamics.

    Science.gov (United States)

    Sheldon, Claire A; Kwon, Young Joon; Liu, Grant T; McCormack, Shana E

    2015-02-01

    Pseudotumor cerebri syndrome (PTCS) is defined by the presence of elevated intracranial pressure (ICP) in the setting of normal brain parenchyma and cerebrospinal fluid (CSF). Headache, vision changes, and papilledema are common presenting features. Up to 10% of appropriately treated patients may experience permanent visual loss. The mechanism(s) underlying PTCS is unknown. PTCS occurs in association with a variety of conditions, including kidney disease, obesity, and adrenal insufficiency, suggesting endocrine and/or metabolic derangements may occur. Recent studies suggest that fluid and electrolyte balance in renal epithelia is regulated by a complex interaction of metabolic and hormonal factors; these cells share many of the same features as the choroid plexus cells in the central nervous system (CNS) responsible for regulation of CSF dynamics. Thus, we posit that similar factors may influence CSF dynamics in both types of fluid-sensitive tissues. Specifically, we hypothesize that, in patients with PTCS, mitochondrial metabolites (glutamate, succinate) and steroid hormones (cortisol, aldosterone) regulate CSF production and/or absorption. In this integrated mechanism review, we consider the clinical and molecular evidence for each metabolite and hormone in turn. We illustrate how related intracellular signaling cascades may converge in the choroid plexus, drawing on evidence from functionally similar tissues.

  3. Complex Interplay between FleQ, Cyclic Diguanylate and Multiple σ Factors Coordinately Regulates Flagellar Motility and Biofilm Development in Pseudomonas putida.</